PMID- 15307183 OWN - NLM STAT- MEDLINE DCOM- 20041007 LR - 20041117 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 34 IP - 9 DP - 2004 Sep TI - Potent T cell response to a class I-binding 13-mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length. PG - 2510-9 AB - 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. CI - Copyright 2004 Wiley-VCH Verlag GmbH & Co. FAU - Green, Kate J AU - Green KJ AD - Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Australia. FAU - Miles, John J AU - Miles JJ FAU - Tellam, Judy AU - Tellam J FAU - van Zuylen, Wendy J M AU - van Zuylen WJ FAU - Connolly, Geoff AU - Connolly G FAU - Burrows, Scott R AU - Burrows SR LA - eng PT - Journal Article PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (BZLF1 protein, Herpesvirus 4, Human) RN - 0 (DNA-Binding Proteins) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-B35 Antigen) RN - 0 (Immunodominant Epitopes) RN - 0 (Peptide Fragments) RN - 0 (Trans-Activators) RN - 0 (Viral Proteins) SB - IM MH - Antigen Presentation MH - Cell Line MH - DNA-Binding Proteins/immunology MH - *Epitopes, T-Lymphocyte MH - HLA-B35 Antigen/*metabolism MH - Herpesvirus 4, Human/*immunology MH - Humans MH - Immunodominant Epitopes MH - Peptide Fragments/*metabolism MH - Polymorphism, Genetic MH - T-Lymphocytes/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Trans-Activators/immunology MH - Viral Proteins/immunology EDAT- 2004/08/13 05:00 MHDA- 2004/10/08 09:00 CRDT- 2004/08/13 05:00 PHST- 2004/08/13 05:00 [pubmed] PHST- 2004/10/08 09:00 [medline] PHST- 2004/08/13 05:00 [entrez] AID - 10.1002/eji.200425193 [doi] PST - ppublish SO - Eur J Immunol. 2004 Sep;34(9):2510-9. doi: 10.1002/eji.200425193.