Potent T cell response to a class I‐binding 13‐mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length
Open Access
- 5 August 2004
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 34 (9), 2510-2519
- https://doi.org/10.1002/eji.200425193
Abstract
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.Keywords
This publication has 28 references indexed in Scilit:
- Longer peptide can be accommodated in the MHC class I binding site by a protrusion mechanismEuropean Journal of Immunology, 2000
- Role of Cytotoxic T Lymphocytes in Epstein-Barr Virus-Associated DiseasesAnnual Review of Microbiology, 2000
- Cytotoxic T cell recognition of allelic variants of HLA B35 bound to an Epstein-Barr virus epitope: influence of peptide conformation and TCR-peptide interactionEuropean Journal of Immunology, 1999
- MECHANISMS OF MHC CLASS I–RESTRICTED ANTIGEN PROCESSINGAnnual Review of Immunology, 1998
- How Selective Is the TransporterAssociated with Antigen Processing?Immunity, 1996
- T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen.The Journal of Experimental Medicine, 1995
- The relative distribution of B35 alleles and their IEF isotypes in a HLA‐B35‐positive populationTissue Antigens, 1995
- Existence of a molecular ruler in proteasomes suggested by analysis of degradation productsFEBS Letters, 1994
- Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middleNature, 1992
- Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 Å resolutionJournal of Molecular Biology, 1991