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 asymptomatic virus carriers has been mapped to four epitope regions in EBV latent cycle Ags. One of these peptide-defined epitopes (RRIYDLIEL) tends to be 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 induce responses only in the context of one subtype, the immunogenic combinations being RRARSLSAERY/B*2702, RRRWRRLTV/B*2704, and FRKAQIQGL/B*2705. We used 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 peptides are identical with the previously identified synthetic sequences. Despite the subtype-specific immunogenicity of three of the four epitopes, all four epitope peptides were found in association with each of the three different HLA-B27 subtypes. Indeed, those peptides that failed to induce a response in the context of a particular HLA-B27 subtype were frequently presented at greater abundance by that subtype than were the immunogenic peptides. Furthermore, among the peptides that did induce a response, immunodominance did not correlate with epitope abundance; in fact the immunodominant RRIYDLIEL epitope was least abundant, being present at less than one copy per cell. The relationship of this unexpected finding to the persistence of EBV is discussed.
Crotzer
V L
VL
Department of Microbiology and the Carter Immunology Center, University of Virginia, Charlottesville 22908, USA.
Christian
R E
RE
Brooks
J M
JM
Shabanowitz
J
J
Settlage
R E
RE
Marto
J A
JA
White
F M
FM
Rickinson
A B
AB
Hunt
D F
DF
Engelhard
V H
VH
D000483:Alleles; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D008213:Lymphocyte Activation; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology
D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen; D016056:Immunodominant Epitopes; D009842:Oligopeptides