HLA-B27 SUBTYPE POLYMORPHISM AND CTL EPITOPE CHOICE - STUDIES WITH EBV PEPTIDES LINK IMMUNOGENICITY WITH STABILITY OF THE B27-PEPTIDE COMPLEX

HLA-B27-restricted CTL responses to EBV are principally directed again st two of the EBV nuclear Ags, EBNAs 3B and 3C. We have previously des cribed a target epitope derived from EBNA 3C (residues 258-266, sequen ce RRIYDLIEL) that is immunodominant in the context of at least three different B27 subtypes, including B2705 and B*2702. In this study, we show that this peptide binds well to B2705 and B*2702 in a cell surf ace binding assay, and that the two B27:peptide complexes are relative ly stable, with t(1/2) of 20 and 37 h, respectively. We now identify a nother B27-restricted epitope derived from EBNA 3B (residues 243-253, sequence RRARSLSAERY), which again accords well with the B2705/B*2702 consensus motifs, having an arginine residue at position 2 and a tyro sine residue at the carboxyl terminus. In this case, five of five B27 02-positive donors respond to the epitope, whereas there was no respon se in any B2705-positive donor studied. This peptide binds at least a s well to B2705 as to its restriction element B*2702; however, the tw o class I:peptide complexes show marked differences in stability, with t(1/2) of 9 and 42 h, respectively. Thus, the stability of B27:peptid e complexes can vary markedly between different B27 subtypes in ways t hat may not be apparent from cell surface binding assays and cannot be predicted from currently known peptide consensus motifs, yet which ma y critically influence CTL epitope choice.