Materials and methods relating to immunogenic epitopes from human papillomavirus

Abstract

Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.

What is claimed is: 
     
         1 . An immune cell comprising a T-cell receptor (TCR) capable of binding a synthetic polypeptide comprising a cytotoxic T lymphocyte (CTL) epitope from an E2 human papillomavirus subtype 16 (HPV16) antigen, the CTL epitope comprising an amino acid sequence selected from VYLTAPTGCI (SEQ ID NO: 6), SPEIIRQHL (SEQ ID NO: 7), VVEGQVDYY (SEQ ID NO: 9), ILTAFNSSHK (SEQ ID NO: 12), HPAATHTKAV (SEQ ID NO: 14), DSAPILTAF (SEQ ID NO: 16), LQDVSLEVY (SEQ ID NO: 17), YLTAPTGCI (SEQ ID NO: 18), QVILCPTSV (SEQ ID NO: 19), NPCHTTKLL (SEQ ID NO: 22), GIRTYFVQF (SEQ ID NO: 23), or YYVHEGIRTY (SEQ ID NO: 24), wherein the CTL epitope is no more than 10 amino acids in length. 
     
     
         2 . A method of detecting an HPV16-associated disease in a subject, the method comprising:
 obtaining a biological sample from a subject, wherein the biological sample comprises T cells;   performing an MHC tetramer assay using the biological sample; and   detecting or quantifying T cells capable of binding a synthetic polypeptide comprising a cytotoxic T lymphocyte (CTL) epitope from an E2 human papillomavirus subtype 16 (HPV16) antigen, the CTL epitope comprising an amino acid sequence selected from VYLTAPTGCI (SEQ ID NO: 6), SPEIIRQHL (SEQ ID NO: 7), VVEGQVDYY (SEQ ID NO: 9), ILTAFNSSHK (SEQ ID NO: 12), HPAATHTKAV (SEQ ID NO: 14), DSAPILTAF (SEQ ID NO: 16), LQDVSLEVY (SEQ ID NO: 17), YLTAPTGCI (SEQ ID NO: 18), QVILCPTSV (SEQ ID NO: 19), NPCHTTKLL (SEQ ID NO: 22), GIRTYFVQF (SEQ ID NO: 23), or YYVHEGIRTY (SEQ ID NO: 24, wherein the CTL epitope is no more than 10 amino acids in length;   wherein the detection or quantification of the T cells indicates the presence of an HPV− 16-associated disease in the subject.   
     
     
         3 . The method of  claim 2 , wherein the at least one synthetic peptide encodes a CTL epitope from the HPV16 E2 antigen, HPV16 E6 antigen, or HPV16 E7 antigen.