Immunodominance among EBV-derived epitopes restricted by HLA-B27 does not correlate with epitope abundance in EBV-transformed B-lymphoblastoid cell lines

Using synthetic peptides, the HLA-B27-restricted CTL response to EBV in asy mptomatic virus carriers has been mapped to four epitope regions in EBV lat ent cycle Ags, One of these peptide-defined epitopes (RRIYDLIEL) tends to b e immunodominant and is recognized in the context of all three B27 subtypes studied, B*2702, B*2704, and B*2705, The other peptide-defined epitopes in duce responses only in the context of one subtype, the immunogenic combinat ions being RRARSLSAERY/B*2702, RRRWRRLTV/B*2704, and FRKAQIQGL/B*2705, We u sed immunoaffinity chromatography to isolate the naturally presented viral peptides associated with these MHC class I molecules on the surface of EBV- transformed B-LCL, Using CTL reconstitution assays in conjunction with mass spectrometry, we established that the naturally processed and presented pe ptides are identical with the previously identified synthetic sequences, De spite the subtype-specific immunogenicity of three of the four epitopes, al l Pour epitope peptides were found in association with each of the three di fferent HLA-B27 subtypes, Indeed, those peptides that failed to induce a re sponse in the context of a particular HLA-B27 subtype were frequently prese nted at greater abundance by that subtype than were the immunogenic peptide s, Furthermore, among the peptides that did induce a response, immunodomina nce did not correlate with epitope abundance; in fact the immunodominant RR IYDLIEL epitope was least abundant, being present at less than one copy per cell. The relationship of this unexpected finding to the persistence of EB V is discussed,