Immunogenic proteins and fragments thereof from allergenic mites

Abstract

The invention relates to novel immunogenic polypeptides identified in house dust mites and storage mites, which have the potential to be used in allergy immunotherapy, for diagnostic purposes, eventually via production of antibodies binding the polypeptide or for characterising allergen extracts of house dust mites and storage mites.

1 . A polypeptide comprising or consisting of
 (a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 31, 291, 1-30, 32-44, 261-290, 292-332, or   (b) an amino acid sequence consisting of at least or exactly 9 contiguous amino acid residues from the amino acid sequence of (a), or   (c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (a), or   (d) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (b).   
     
     
         2 . The polypeptide according to  claim 1 , wherein the sequence identity in option (c) is at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. 
     
     
         3 . The polypeptide according to any one of  claim 1  or  2 , wherein the polypeptide of option (c) has the same biological activity or functionality as the polypeptide of option (a) for example, the same enzymatic functionality, optionally the same, greater or less ability to elicit, stimulate or induce an immune response (e.g. in vitro T cell proliferation or T cell cytokine production, such as the cytokines, IL-4, IL-5, IL-13 and/or IL-10) in blood from a mite allergic individual; optionally the same, greater or less ability to induce immunological tolerance against mites, a mite allergen or the polypeptide of option (a) and/or to bind or interact with IgE, IgG or IgA antibodies raised against the polypeptide of option (a). 
     
     
         4 . The polypeptide according to  claim 1 , wherein the at least or exactly 9 contiguous amino acid residues of option (b) or (d) constitute at least or exactly or at most 10, at least or exactly or at most 11, at least or exactly or at most 12, at least or exactly or at most 13, at least or exactly or at most 14, at least or exactly or at most 15, at least or exactly or at most 16, at least or exactly or at most 17, at least or exactly or at most 18, at least or exactly or at most 19, at least or exactly or at most 20, at least or exactly or at most 21, at least or exactly or at most 22, at least or exactly or at most 23, at least or exactly or at most 24, at least or exactly or at most 25, at least or exactly or at most 26, at least or exactly or at most 27 at least or exactly or at most 28, at least or exactly or at most 29, at least or exactly or at most 30, at least or exactly or at most 31, at least or exactly or at most 32, at least or exactly or at most 33, at least or exactly or at most 34, at least or exactly or at most 35, at least or exactly or at most 36, at least or exactly or at most 37, at least or exactly or at most 38, at least or exactly or at most 39, at least or exactly or at most 40, at least or exactly or at most 41, at least or exactly or at most 42, at least or exactly or at most 43, at least or exactly or at most 44, at least or exactly or at most 45, at least or exactly or at most 46, at least or exactly or at most 47, at least or exactly or at most 48, at least or exactly or at most 49, at least or exactly or at most 50, at least or exactly or at most 51, at least or exactly or at most 52, at least or exactly or at most 53, at least or exactly or at most 54, at least or exactly or at most 55, at least or exactly or at most 56, at least or exactly or at most 57, at least or exactly or at most 58, at least or exactly or at most 59, at least or exactly or at most 60, at least or exactly or at most 61, at least or exactly or at most 62, at least or exactly or at most 63, at least or exactly or at most 64, at least or exactly or at most 65, at least or exactly or at most 66, at least or exactly or at most 67, at least or exactly or at most 68, at least or exactly or at most 69, at least or exactly or at most 70, at least or exactly or at most 71, at least or exactly or at most 72, at least or exactly or at most 73, at least or exactly or at most 74, at least or exactly or at most 75, at least or exactly or at most 76, at least or exactly or at most 77, at least or exactly or at most 78, at least or exactly or at most 79, at least or exactly or at most 80, at least or exactly or at most 81, at least or exactly or at most 82, at least or exactly or at most 83, at least or exactly or at most 84, at least or exactly or at most 85, at least or exactly or at most 86, at least or exactly or at most 87, at least or exactly or at most 88, at least or exactly or at most 89, at least or exactly or at most 90, at least or exactly or at most 91, at least or exactly or at most 92, at least or exactly or at most 93, at least or exactly or at most 94, at least or exactly or at most 95, at least or exactly or at most 96, at least or exactly or at most 97, at least or exactly or at most 98, at least or exactly or at most 99, at least or exactly or at most 100, at least or exactly or at most 101, at least or exactly or at most 102, at least or exactly or at most 103, at least or exactly or at most 104, at least or exactly or at most 105, at least or exactly or at most 106, at least or exactly or at most 107, at least or exactly or at most 108, at least or exactly or at most 109, at least or exactly or at most 110, at least or exactly or at most 111, at least or exactly or at most 112, at least or exactly or at most 113, at least or exactly or at most 114, at least or exactly or at most 115, at least or exactly or at most 116, at least or exactly or at most 117, at least or exactly or at most 118, at least or exactly or at most 119, at least or exactly or at most 120, at least or exactly or at most 121, at least or exactly or at most 122, at least or exactly or at most 123, or at least or exactly or at most 124 amino acid residues. 
     
     
         5 . The polypeptide according to any one of  claim 1  or  4 , wherein the contiguous amino acid residues of option (b) or (d) commence
 at amino acid residue 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, or 117 in any one of SEQ ID NOs: 1-44 and 261-332; or 
 at amino acid residue 118, 119, 120, 121, or 122 in any one of SEQ ID NOs: 1-44, 261-304, 306-318, and 320-332; or 
 at amino acid residue 123 or 124 in any one of SEQ ID NOs: 2-44, 262-304, 306-318, and 320-332; or 
 at amino acid residue 125 or 126 in any one of SEQ ID NOs: 4-44, 264-304, 306-318, and 320-332; or 
 at amino acid residue 127, 128, or 129 in any one of SEQ ID NOs: 5-44, 265-304, 306-318, and 320-332; or 
 at amino acid residue 130, 131, 132, 133, 134, 135, 136, 135, 136, 137, 138, 139, 140, 141, 142 in any one of SEQ ID NOs: 5-44, 265-304, 306-314, 316-318, 320-328, and 330-332; or 
 at amino acid residue, 143 or 144 in any one of SEQ ID NOs: 5-44, 265-304, 306-313, 316-318, 320-327, and 330-332; or 
 at amino acid residue 145 and 146 in any one of SEQ ID NOs: 7-44, 267-304, 306-313, 316-318, 320-327, and 330-332; or 
 at amino acid residue 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, or 163 in any one of SEQ ID NOs: 9-44, 269-304, 306-313, 316-318, 320-327, and 330-332; or 
 at amino acid residue 164 in any one of SEQ ID NOs: 10-44, 270-304, 306-313, 316-318, 320-327, and 330-332; or 
 at amino acid residue 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178 in any one of SEQ ID NOs: 11-44, 271-304, 306-313, 316-318, 320-327, and 330-332; or 
 at amino acid residue 179 or 180 in any one of SEQ ID NOs: 11-44 and 271-304, 306-313, 316-317, 320-327, and 330-331; or 
 at amino acid residue 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, or 214 in any one of SEQ ID NOs: 13-44, 273-304, 306-313, 316-317, 320-327, and 330-331; or 
 at amino acid residue 215, 216, 217, 218, 219, or 220 in any one of SEQ ID NOs: in any one of SEQ ID NOs: 15-44, 275-304, 306-313, 316-317, 320-327, and 330-331; or 
 at amino acid residue 221 in any one of SEQ ID NOs: 17-44 and 275-304; or 
 at amino acid residue 222, 223, or 224 in any one of SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 316-317, 320-327, and 330-331; or 
 at amino acid residue 225 in any one of SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 317, 320-327, and 331; or 
 at amino acid residue 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, or 244 in any one of SEQ ID NOs: 19-44, 279-304, 306-313, 317, 320-327, and 331; or 
 at amino acid residue 245 in any one of SEQ ID NOs: 20-44, 280-304, 306-313, and 320-327; or 
 at amino acid residue 246, 247, 248, 249, 250, 251, or 252 in any one of SEQ ID NOs: 21-44 and 281-304, 306-313, and 320-327; or 
 at amino acid residue 253 in any one of SEQ ID NOs: 21-44, 281-304, 306-312, and 320-326; or 
 at amino acid residue 254 in any one of SEQ ID NOs: 22-44 and 282-304; or 
 at amino acid residue 255, 256, 257, 258, 259, 260, 261, or 262 in any one of SEQ ID NOs: 23-44, 283-304, 306-312, and 320-326; or 
 at amino acid residue 263 in any one of SEQ ID NOs: in any one of SEQ ID NOs: 24-44, 284-304, 306-312, and 320-326; or 
 at amino acid residue 264, 265, 266, or 267 in any one of SEQ ID NOs: 25-44, 285-304, 306-312, and 320-326; or 
 at amino acid residue 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301 in any one of SEQ ID NOs: 26-44, 286-304, 306-312, and 320-326; or 
 at amino acid residue 302 in any one of SEQ ID NOs: 26-44, 286-304, 306-311, and 320-325; or 
 at amino acid residue, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313 in any one of SEQ ID NOs: 27-44, 287-304, 306-311, and 320-325; or 
 at amino acid residue 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, or 324 in any one of SEQ ID NOs: 28-44, 288-304, 306-311, and 320-325; or 
 at amino acid residue 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, or 353 in any one of SEQ ID NOs: 30-44, 290-304, 306-311, and 320-325; or 
 at amino acid residue 354 in any one of SEQ ID NOs: 31-44 291-304, 306-311, and 320-325; or 
 at amino acid residue 355 in any one of SEQ ID NOs: 32-44 292-304, 306-311, and 320-325; or 
 at amino acid residue 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, or 421 in any one of SEQ ID NOs: 32-44, 292-304, 307-311, and 321-325; or 
 at amino acid residue 422, 423, 424, 425, or 426 in any one of SEQ ID NOs: 33-44, 293-304, 307-311, and 321-325; or 
 at amino acid residue 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451 in any one of SEQ ID NOs: 34-44, 294-304, 307-311, and 321-325; or 
 at amino acid residue 452, 453, or 454 in any one of SEQ ID NOs: 34-44, 294-304, 307-310, and 321-324; or 
 at amino acid residue 455 in any one of SEQ ID NOs: 36-44, 296-304, 307-310, and 321-324; or 
 at amino acid residue 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, or 466 in any one of SEQ ID NOs: 37-44, 297-304, 307-310, and 321-324; or 
 at amino acid residue 467, 468, 469, 470, 471, 472, 473, or 474 in any one of SEQ ID NOs: 38-44, 298-304, 307-310, and 321-324; or 
 at amino acid residue 475, 476, 477, 478, 479, 480, 481, 482, or 483 in any one of SEQ ID NOs: 38-44, 298-304, 307, 308, 310, 321, 323, and 324; or 
 at amino acid residue 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, or 501 in any one of SEQ ID NOs: 38-44, 298-304, 307, 308, 321, and 323; or 
 at amino acid residue 502, 503, 504, 505, 506, 507, 508, 509, 510, or 511 in any one of SEQ ID NOs: 39-44, 299-304, 307, 308, 321, and 323; or 
 at amino acid residue 512 in any one of SEQ ID NOs: 39, 41-44, 299, 301-304, 307, 308, 321, and 323; or 
 at amino acid residue 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, or 877 in any one of SEQ ID NOs: 41-44 301-304, 307, 308, 321, and 323; or 
 at amino acid residue 878 or 879 in any one of SEQ ID NOs: 41, 43, 44, 301, 303, 304, 307, 308, 321, and 323; or 
 at amino acid residue 880 or 881 in any one of SEQ ID NOs: 43, 44, 303, 304, 307, 308, 321, and 323; or 
 at amino acid residue, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965 in any one of SEQ ID NOs: 43, 44, 303, 304, 307, and 321; or 
 at amino acid residue, 966 or 967 in any one of SEQ ID NOs: 43, 44, 303, and 304; or 
 
       at amino acid residue 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, or 982 in SEQ ID NO: 44 or 304; with the proviso that the number, N, of the commencing amino residue satisfies the formula N≤L−n+1, where L is the number of amino acid residues in the sequence among SEQ ID NOs: 1-44 and 261-332 from which the commencing residue is selected, and n is the number of consecutive amino acid residues. 
     
     
         6 . The polypeptide according to any one of  claims 1 ,  4  and  5 , wherein the sequence identity in option (d) is at least 60%, such as at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. 
     
     
         7 . The polypeptide according to any one of  claims 1 ,  4 - 6 , wherein the polypeptide of option (d) may have the same biological activity or functionality as the polypeptide of option (b), for example, it may have the same enzymatic functionality, it may have the same, greater or less ability to elicit, stimulate or induce an immune response (e.g. in vitro T cell proliferation or T cell cytokine production (for example the cytokines, IL-4, IL-5, IL-13 and/or IL-10) in blood of a mite allergic individual; to induce immunological tolerance against mites, mite allergens or the polypeptide of option (b); and/or to bind or interact with IgE, IgG or IgA antibodies raised against the polypeptide of option (b). 
     
     
         8 . The polypeptide according to any one of  claims 1 ,  4 - 7 , wherein the polypeptide of option (b) and (d) has a length of 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid residues. 
     
     
         9 . The polypeptide according to  claim 8 , wherein the polypeptide of option (d) has greater or less ability to bind a Class HLA II allele or a group of Class HLA II alleles than the parent polypeptide of option (b), for example, the polypeptide of option (d) may bind to at least 70%, such as at least 75%, 80%, 85%, 90% or 95% of the Class HLA II alleles that the parent polypeptide of option (b) binds to. 
     
     
         10 . The polypeptide according to any one of  claims 1 ,  4 - 9 , wherein the consecutive amino acids of option (b) and (d) comprise a T cell epitope, optionally a Th2 cell epitope. 
     
     
         11 . The polypeptide according to any one of the preceding claims, which comprises or consists of an amino acid sequence consisting of
 a) 9, 10, 11, 12, 13, 14 or 15 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260 and any one of SEQ ID NOs: 45, 61, 63, 80, 100, 113, 147, 154, 170, 172, 191, 215, 225, 226, 248, and 260, wherein any cysteine residue is/are substituted with a serine residue, an alanine residue or a 2-aminobutyric acid residue, or   b) a variant of 9 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or   c) a variant of 10 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or   d) a variant of 11 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or   e) a variant of 12 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or   f) a variant of 13 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, or 5 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or   g) a variant of 14 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, or 5 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence   h) a variant of a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, 5, or 6 amino acids are substituted with a different amino acid in the variant relative to the parent polypeptide sequence.   
     
     
         12 . The polypeptide according to  claim 11 , wherein the parent polypeptide sequence commences at
 residue 1, 2, 3, 4, 5, 6, or 7 in any one of SEQ ID NOs: 45-260 when the peptide is 9 amino acids in length, or   residue 1, 2, 3, 4, 5, or 6 in any one of SEQ ID NOs: 45-260 when the peptide is 10 amino acids in length, or   residue 1, 2, 3, 3, 4, or 5 in any one of SEQ ID NOs: 45-260 when the peptide is 11 amino acids in length, or   residue 1, 2, 3, or 4 in any one of SEQ ID NOs: 45-260 when the peptide is 12 amino acids in length, or   residue 1, 2, or 3 in any one of SEQ ID NOs: 45-260 when the peptide is 13 amino acids in length, or   residue 1 or 2 in any one of SEQ ID NOs: 45-260 when the peptide is 14 amino acids in length.   
     
     
         13 . The polypeptide according to any one of  claims 11  and  12 , wherein the polypeptide of option a) to h) comprises a T cell epitope, optionally a Th2 cell epitope. 
     
     
         14 . The polypeptide according to any one of  claims 11 - 13 , which comprises any one of SEQ ID NOs: 45-260. 
     
     
         15 . The polypeptide according to any one of  claims 11 - 14 , wherein the polypeptide has a length of 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid residues. 
     
     
         16 . The polypeptide according to any one of the preceding claims, which is able to cross-react with any one of SEQ ID NOs: 1-260 when tested in a T-cell proliferation assay employing T cells from a patient allergic to the mites or the protein allergens. 
     
     
         17 . The polypeptide according to any one of the preceding claims, which consists of an amino acid sequence identical with the amino acid sequence of a proteolytic fragment of a protein consisting of an amino acid sequence selected from any one of SEQ ID NOs: 1-44, and 261-332, preferably from any one of SEQ ID NOs: 1-44 and 305-318. 
     
     
         18 . The polypeptide according to  claim 17 , wherein the proteolytic fragment is a tryptic or chymotryptic fragment. 
     
     
         19 . The polypeptide according to  claim 17  or  18 , which includes a mass modifying label. 
     
     
         20 . The polypeptide according to any one of the preceding claims, which comprises at least one of the following modifications:
 a)N-terminal acetylation or methylation   b) C terminal amidation   c)C-terminal amination   d) addition of one to three charged amino acid residues selected from any one of lysine (K), arginine (R), aspartic acid (D), and glutamic acid (E) in the N-terminal or C-terminal   e) replacement of one or more hydrogen(s) on the side chain amines of arginine and/or lysine with a methylene group   f) glycosylation, and   g) phosphorylation.   
     
     
         21 . A composition, such as a pharmaceutical composition, comprising one or more of the polypeptides according to any one of the preceding claims. 
     
     
         22 . The pharmaceutical composition according to  claim 21 , further comprising a pharmaceutically acceptable carrier, excipient, and/or adjuvant, optionally sterile. 
     
     
         23 . The pharmaceutical composition according to  claim 21  or  22  formulated as a vaccine for parenteral administration. 
     
     
         24 . The pharmaceutical composition according to any one of  claims 21 - 23 , wherein the pharmaceutical composition is a powder, optionally formulated to be re-dissolved before use. 
     
     
         25 . A method of treating allergy in a patient, where signs and/or symptoms of said allergy are elicited in the patient by exposure to house dust mites or storage mites and/or exposure to at least one protein allergen present in house dust mites or storage mites, the method comprising administering, to the patient, a therapeutically effective amount of a polypeptide according to any one of  claims 1 - 20  or the composition according to any one of  claims 21 - 24 . 
     
     
         26 . The method according to  claim 25 , wherein exposure of the patient to the polypeptide does not elicit signs or symptoms of allergy in the patient. 
     
     
         27 . The method according to  claim 25  or  26 , wherein exposure of the patient to one or more protein(s) having an amino acid sequence consisting of or comprising an amino acid sequence selected from SEQ ID NOs: 1-44 or 261-304 does not elicit signs of allergy (i.e. IgE-mediated allergy) in the patient. 
     
     
         28 . The method according to any one of  claims 25 - 27 , wherein treating the allergy comprises or consists of relieving or reducing an immune response triggered by exposure to the mites or the protein allergen. 
     
     
         29 . The method according to any one of  claims 25 - 28 , wherein treating the allergy comprises or consists of relieving one or more symptoms of an immune response triggered by exposure to the mites or the protein allergen. 
     
     
         30 . The method according to any one of  claims 25 - 29 , wherein treating the allergy consists of or comprises inducing immunological tolerance against the mites or the protein allergen. 
     
     
         31 . The method according to any one of  claims 25 - 30 , wherein treating the allergy comprises or consists of relieving one or more symptom(s) associated with allergic rhinitis and/or allergic conjunctivitis and/or allergic asthma and/or allergic eczema (e.g. atopic dermatitis). 
     
     
         32 . The method according to any one of  claims 25 - 31 , wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic rhinitis, such as
 reducing the intensity of itchy nose and/or   reducing the number of sneezes within a given period (e.g. daily, weekly, monthly) and/or   reducing the intensity of blocked nose (congestion) and/or   reducing the amount of nasal fluid and/or   reducing the eosinophilic count in nasal fluid and/or   reducing specific IgE antibody level (titre) in nasal fluid or in serum and/or   reducing basophil histamine release in blood.   
     
     
         33 . The method according to any one of  claims 25 - 32 , wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic conjunctivitis, such as
 reducing the intensity of itchy eyes, redness in the white of the eyes and/or watery eyes; and/or   reducing the eosinophilic count in conjunctival tissue scrapings; and/or   reducing specific IgE antibody level (titer) in conjunctival tissue scrapings or in serum; and/or   reducing basophil histamine release in blood.   
     
     
         34 . The method according to any one of  claims 25 - 33 , wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic asthma, such as
 reducing the intensity and/or number of coughs within a given period (e.g. daily, weekly, monthly); and/or   reducing the intensity of wheezes; and/or   improving being short of breath; and/or   improving lung function; and/or   reducing specific IgE antibody level (titre) in lung fluid or in serum; and/or   reducing basophil histamine release in blood.   
     
     
         35 . The method according to any one of  claims 25 - 34 , wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with atopic dermatitis, such as
 reducing itch intensity of the skin; and/or   reducing eczema score; and/or   reducing number of (peripheral) blood eosinophils.   
     
     
         36 . The method according to any one of  claims 25 - 35 , comprising or consisting of reducing the patient's need for concomitant treatment with corticosteroids or H1 antihistamines to reduce, relieve or suppress one or more symptoms of an immune response associated with the allergy. 
     
     
         37 . The method according to  claim 36 , wherein the immune response is clinically presented as atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anaphylaxis, and/or hay fever. 
     
     
         38 . The method according to  claim 36  or  37 , wherein the method decreases, reduces, suppresses or inhibits atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anaphylaxis, and/or hay fever. 
     
     
         39 . The method according to any one of  claims 25 - 38 , comprising inducing or increasing an IgG antibody response in the patient to a protein allergen of the mites and/or decreasing an IgE antibody response in the patient to a protein allergen of the mites and/or decreasing a T cell response in the patient against a protein allergen of the mites. 
     
     
         40 . The method according to any one of  claims 25 - 39 , wherein the patient is sensitized to at least one protein allergen of the mites. 
     
     
         41 . The method according to any one of  claims 25 - 40 , wherein the mites are house dust mites of the genus  Dermatophagoides  (for example selected from the group consisting of  Dermatophagoides pteronyssinus, Dermatophagoides farinae ) or of the genus  Euroglyphus  (for example  Euroglyphus maynei ), or wherein the mites are storage mites of the genus  Glycyphagus, Lepidoglyphus, Tyrophagus , or  Blomia  (for example  Glycyphagus domesticus, Lepidoglyphus  destructor,  Tyrophagus putrescentiae , or  Blomia tropicalis ). 
     
     
         42 . The method according to any one of  claims 25 - 41 , wherein the protein allergen is selected from one or more protein allergens in the groups consisting of
 a group 1 allergen of mites (for example a group 1 allergen of a house dust mite (e.g. Der p 1, Der f 1, or Eur m 1, or a group 1 allergen of a storage mite, e.g. Gly d 1, Lep d 1, Typ p 1 and Blo t 1) and   a group 2 allergen of mites (for example a group 2 allergen of a house dust mite, e.g. Der p 2, Der f 2 and Eur m 2, and a group 2 allergen of a storage mite, e.g. Gly d 2, Lep d 2, Typ p 2 and Blo t 2).   
     
     
         43 . The method according to any one of  claims 25 - 42 , wherein the signs or symptoms of allergy not elicited by the polypeptide are one or more signs or symptoms selected from the group consisting of:
 the presence in the patient of specific IgE antibodies that binds to the immunogen;   a positive skin prick test with the polypeptide; and   the signs or symptoms defined in any one of  claims 31 - 35 .   
     
     
         44 . An in vitro method of determining whether T cells of a subject are responsive to one or more of the polypeptides according to any one of  claims 1 - 20  and/or the composition according to any one of  claims 21 - 24 , comprising a step of contacting T cells obtained from the subject with said polypeptide(s) or composition and detecting whether the T cells are stimulated. 
     
     
         45 . An in vitro method of diagnosing a subject for sensitization to (allergy to) house dust mites or storage mites, comprising a step of contacting T cells obtained from the subject with one or more of the polypeptides according to any one of  claims 1 - 20  and/or the composition according to any one of  claims 21 - 24  and detecting whether the T cells are stimulated. 
     
     
         46 . An in vitro method for determining whether a subject has, or is at risk of developing, an allergy to house dust mites or storage mites, comprising a step of contacting T cells obtained from the subject with one or more of the polypeptides according to any one of  claims 1 - 20  and/or the composition according to any one of  claims 21 - 24  and detecting whether the T cells are stimulated. 
     
     
         47 . A diagnostic kit comprising one or more of the polypeptides according to any one of  claims 1 - 20  and/or the composition according to any one of  claims 21 - 24 . 
     
     
         48 . An isolated nucleic acid fragment, which comprises
 i) a nucleotide sequence encoding a polypeptide according to any one of  claims 1 - 20 , or   ii) a nucleotide sequence complementary to the nucleotide sequence in i).   
     
     
         49 . The nucleic acid fragment according to  claim 48 , which is a DNA or an RNA fragment. 
     
     
         50 . A vector comprising the nucleic acid fragment according to  claim 48 , such as a cloning vector or an expression vector. 
     
     
         51 . The vector according to  claim 50 , which comprises in operable linkage and in the 5′-3′ direction, an expression control region comprising an enhancer/promoter for driving expression of the nucleic acid fragment defined in  claim 48 - i ), optionally a signal peptide coding sequence, a nucleotide sequence defined in  claim 48 - i ), and optionally a terminator. 
     
     
         52 . The vector according to  claim 51 , wherein the expression control region drives expression in prokaryotic cell such as a bacterium, e.g. in  E. coli.    
     
     
         53 . The vector according to claim any one of  claims 50 - 52 , which is capable of autonomous replication. 
     
     
         54 . The vector according to any one of  claims 50 - 53 , which is capable of being integrated into the genome of a host cell. 
     
     
         55 . The vector according to any one of  claims 50 - 54 , which is selected from the group consisting of a virus, such as an attenuated virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid. 
     
     
         56 . A cell which is transformed to carry the vector according to any one of  claims 50 - 55 . 
     
     
         57 . The transformed cell according to  claim 56 , which is capable of replicating the nucleic acid fragment defined in  claim 48 - i ) and/or which is capable of expressing the nucleic acid fragment defined in  claim 48 - i ). 
     
     
         58 . The transformed cell according to  claim 56  or  57 , which is selected from a prokaryotic cell and a eukaryotic cell. 
     
     
         59 . The transformed cell according to any one of  claims 56 - 58 , which is a bacterial cell selected from the group consisting of  Escherichia  (such as  E. coli .),  Bacillus  (e.g.  Bacillus subtilis ),  Salmonella , and  Mycobacterium , preferably non-pathogenic, e.g.  M. bovis  BCG. 
     
     
         60 . The transformed cell according to any one of  claims 56 - 59 , which is stably transformed by having the nucleic acid defined in  claim 48 - i ) stably integrated into its genome. 
     
     
         61 . The transformed cell according to any one of  claims 56 - 60 , which secretes or carries on its surface the polypeptide according to any one of  claims 1 - 20 . 
     
     
         62 . The transformed cell according to  claim 61 , wherein the cell is a bacterium and secretion is into the periplasmic space. 
     
     
         63 . A cell line derived from the transformed cell according to any one of  claims 56 - 62 . 
     
     
         64 . A method for the preparation of the polypeptide according to any one of  claims 1 - 20 , comprising
 culturing a transformed cell according to any of  claims 56 - 62  or the cell line according to  claim 63  under conditions that facilitate that the transformed cell expresses the nucleic acid fragment according to  claim 48 - i ) and subsequently recovering said polypeptide, or   preparing said polypeptide by means of solid or liquid phase peptide synthesis.   
     
     
         65 . An isolated polyclonal antibody, which has been raised against the polypeptide according to any one of  claims 1 - 20 . 
     
     
         66 . A monoclonal antibody or a fragment or analogue thereof, which specifically binds the polypeptide according to any one of  claims 1 - 20  wherein said fragment or analogue comprises at least the variable regions of the antigen binding site of said monoclonal antibody. 
     
     
         67 . A method for qualitative or quantitative determination of the presence in a sample of the polypeptide according to any one of  claims 1 - 20 , the method comprising any one of the following approaches:
 contacting the sample with an antibody according to any one of  claim 65  or  66  and detecting specific binding of material in said sample to said antibody,   contacting the sample with a system comprising a solid phase with an antibody according to  claim 65  or  66  coupled thereto and comprising a labelled polypeptide according to any one of  claims 1 - 20 , where said labelled polypeptide specifically binds said antibody, and gauging the degree of competition exerted by material in the sample on the binding between said labelled polypeptide and said antibody,   contacting the sample with a system comprising 1) a solid phase with a polypeptide according to any one of  claims 1 - 20  coupled thereto and comprising 2) a labelled antibody according to  claim 65  or  66 , where said polypeptide specifically binds said labelled antibody, and gauging the degree of competition exerted by material in the sample on the binding between said polypeptide and said antibody,   subjecting polypeptide material from the sample to proteolytic treatment and subjecting the thus obtained material to quantitative MS, optionally using at least one polypeptide according to any one of  claims 17 - 19  as standard calibration peptide.