title: HLA-B27 subtype polymorphism and CTL epitope choice: studies with EBV peptides link immunogenicity with stability of the B27:peptide complex.
abstract: HLA-B27-restricted CTL responses to EBV are principally directed against two of the EBV nuclear Ags, EBNAs 3B and 3C. We have previously described a target epitope derived from EBNA 3C (residues 258-266, sequence RRIYDLIEL) that is immunodominant in the context of at least three different B27 subtypes, including B*2705 and B*2702. In this study, we show that this peptide binds well to B*2705 and B*2702 in a cell surface binding assay, and that the two B27:peptide complexes are relatively stable, with t1/2 of 20 and 37 h, respectively. We now identify another B27-restricted epitope derived from EBNA 3B (residues 243-253, sequence RRARSLSAERY), which again accords well with the B*2705/B*2702 consensus motifs, having an arginine residue at position 2 and a tyrosine residue at the carboxyl terminus. In this case, five of five B*2702-positive donors respond to the epitope, whereas there was no response in any B*2705-positive donor studied. This peptide binds at least as well to B*2705 as to its restriction element B*2702; however, the two class I:peptide complexes show marked differences in stability, with t1/2 of 9 and 42 h, respectively. Thus, the stability of B27:peptide complexes can vary markedly between different B27 subtypes in ways that may not be apparent from cell surface binding assays and cannot be predicted from currently known peptide consensus motifs, yet which may critically influence CTL epitope choice.
authors.affiliation: CRC Institute for Cancer Studies, University of Birmingham, United Kingdom. Brooksjm@cancer.bham.ac.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Brooks
authors.forename: R A
authors.initials: RA
authors.lastname: Colbert
authors.forename: J P
authors.initials: JP
authors.lastname: Mear
authors.forename: A M
authors.initials: AM
authors.lastname: Leese
authors.forename: A B
authors.initials: AB
authors.lastname: Rickinson
mesh_terms: D017951:Antigen Presentation / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D046911:Macromolecular Substances; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014162:Transfection / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015796:HLA-B27 Antigen; D046911:Macromolecular Substances; D009842:Oligopeptides; D014764:Viral Proteins