Potent T cell response to a class I-binding 13-mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length.
The BZLF1 antigen of Epstein-Barr virus includes three overlapping sequences of different lengths that conform to the binding motif of human leukocyte antigen (HLA) B*3501. These 9-mer (56LPQGQLTAY64), 11-mer (54EPLPQGQLTAY64), and 13-mer (52LPEPLPQGQLTAY64) peptides all bound well to B*3501; however, the CTL response in individuals expressing this HLA allele was directed strongly and exclusively towards the 11-mer peptide. In contrast, EBV-exposed donors expressing HLA B*3503 showed no significant CTL response to these peptides because the single amino acid difference between B*3501 and B*3503 within the F pocket inhibited HLA binding by these peptides. The extraordinarily long 13-mer peptide was the target for the CTL response in individuals expressing B*3508, which differs from B*3501 at a single position within the D pocket (B*3501, 156Leucine; B*3508, 156Arginine). This minor difference was shown to enhance binding of the 13-mer peptide, presumably through a stabilizing interaction between the negatively charged glutamate at position 3 of the peptide and the positively charged arginine at HLA position 156. The 13-mer epitope defined in this study represents the longest class I-binding viral epitope identified to date as a minimal determinant. Furthermore, the potency of the response indicates that peptides of this length do not present a major structural barrier to CTL recognition.
Green
Kate J
KJ
Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Australia.
Miles
John J
JJ
Tellam
Judy
J
van Zuylen
Wendy J M
WJ
Connolly
Geoff
G
Burrows
Scott R
SR
D017951:Antigen Presentation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D010446:Peptide Fragments / Q000378:metabolism*; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D015534:Trans-Activators; D014764:Viral Proteins