US2008064859A1PendingUtilityA1

Recombinant MHC molecules useful for manipulation of antigen-specific T-cells

Individually held — no corporate assignee on recordPriority: Sep 16, 1997Filed: Mar 21, 2007Published: Mar 13, 2008
Est. expirySep 16, 2017(expired)· nominal 20-yr term from priority
C07K 14/70539A61P 37/04A61K 38/00G01N 33/56972G01N 33/56977C07K 2319/00A61P 37/02A61P 43/00
62
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Claims

Abstract

Two-domain MHC polypeptides useful for manipulation of antigen-specific T-cells are disclosed. These polypeptides include MHC class II-based molecules that comprise covalently linked β1 and α1 domains, and MHC class I-based molecules that comprise covalently linked α1 and α2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, and to treat conditions mediated by antigen-specific T-cells.

Claims

exact text as granted — not AI-modified
1 - 35 . (canceled)  
     
     
         35 . A single chain class II MHC molecule comprising: a peptide-binding groove and covalently linked in sequence: 1) a class II beta chain, 2) a single chain linker, and 3) a class II alpha chain, wherein the chain of both 1) and 3) lack a transmembrane domain; and further wherein the single chain class II MHC molecule is empty.  
     
     
         36 . The MHC molecule of  claim 35 , wherein the MHC molecule is soluble.  
     
     
         37 . The MHC molecule of  claim 35 , wherein the chain of 1) comprises a beta domain and the chain of 3) comprises an alpha 1 domain.  
     
     
         38 . The MHC molecule of  claim 35 , wherein the single chain linker is linked between the carboxyl terminus of the beta chain and the amino terminus of the alpha chain.  
     
     
         39 . The MHC molecule of  claim 35 , wherein the beta and alpha chains are each independently selected from the group consisting of IE, IA, DR, DQ and DP proteins.  
     
     
         40 . The MHC molecule of  claim 35 , wherein the MHC molecule is modified to carry a detectable tag.  
     
     
         41 . A multivalent MHC complex comprising two or more linked MHC molecules of  claim 35 .  
     
     
         42 . A MHC complex of  claim 41 , wherein the MHC molecules are linked to immunoglobulin domains.  
     
     
         43 . A MHC complex of  claim 41 , wherein the MHC complex is modified to carry a detectable tag.  
     
     
         44 . A single chain MHC class II-peptide complex comprising: a peptide-binding groove; covalently linked in sequence: 1) a class II beta chain, 2) a single chain linker, and 3) a class II alpha chain, wherein the chain of both 1) and 3) lack a transmembrane domain; and a presenting peptide being covalently linked to the MHC molecule and non-covalently bound to the peptide binding groove of the MHC molecule.  
     
     
         45 . The MHC complex of  claim 44 , wherein the complex is soluble.  
     
     
         46 . The MHC complex of  claim 44 , wherein the chains of 1) and 3) comprise a beta 1 domain and alpha1 domain, respectively.  
     
     
         47 . The MHC complex of  claim 44 , wherein the MHC class II molecule comprises the presenting peptide covalently linked to the .beta. chain.  
     
     
         48 . The MHC complex of  claim 44 , wherein a presenting peptide linker sequence is interposed between the presenting peptide and the MHC molecule.  
     
     
         49 . The MHC complex of  claim 44 , wherein the beta and alpha chains are each independently selected from the group consisting of IE, IA, DR, DQ and DP proteins.  
     
     
         50 . The MHC complex of  claim 44 , wherein the MHC molecule is modified to carry a detectable tag.  
     
     
         51 . A multivalent MHC complex comprising two or more linked MHC molecules of  claim 44 .  
     
     
         52 . The MHC complex of  claim 51 , wherein the MHC molecules are linked to immunoglobulin domains.  
     
     
         53 . The MHC complex of  claim 51 , wherein the MHC complex is modified to carry a detectable tag.  
     
     
         54 . A loaded single chain MHC class II-peptide complex comprising: a peptide-binding groove; covalently linked in sequence: 1) a class II beta chain, 2) a single chain linker, and 3) a class II alpha chain, wherein the chain of both 1) and 3) lack a transmembrane domain; and a presenting peptide being non-covalently linked to the MHC molecule and non-covalently bound to the peptide binding groove of the MHC molecule, wherein the loaded single chain MHC class II-peptide complex can be recognized by a CD4+ T cell.  
     
     
         55 . The MHC complex of  claim 54 , wherein the MHC molecule is soluble.  
     
     
         56 . The MHC complex of  claim 54 , wherein the chain of 1) comprises a beta 1 domain and the chain of 3) comprises an alpha 1 domain.  
     
     
         57 . The MHC complex of  claim 54 , wherein the single chain linker is linked between the carboxyl terminus of the beta chain and the amino terminus of the alpha chain.  
     
     
         58 . The MHC complex of  claim 54 , wherein the beta and alpha chains are each independently selected from the group consisting of IE, IA, DR, DQ and DP proteins.  
     
     
         59 . The MHC complex of  claim 54 , wherein the MHC molecule is modified to carry a detectable tag.  
     
     
         60 . A multivalent MHC complex comprising two or more linked MHC complexes of  claim 54 .  
     
     
         61 . The multivalent MHC complex of  claim 60 , wherein the MHC complexes are linked to immunoglobulin domains.  
     
     
         62 . A multivalent MHC complex of  claim 60 , wherein the MHC complex is modified to carry a detectable tag.

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