PMID- 20566715 OWN - NLM STAT- MEDLINE DCOM- 20100730 LR - 20240109 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 207 IP - 7 DP - 2010 Jul 5 TI - Allelic polymorphism in the T cell receptor and its impact on immune responses. PG - 1555-67 LID - 10.1084/jem.20100603 [doi] AB - In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01(+) public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2beta loop (Gln55-->His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55-->Ala55) in complex with HLA-B*3501(HPVGEADYFEY) revealed that the Gln55-->His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection. FAU - Gras, Stephanie AU - Gras S AD - The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. FAU - Chen, Zhenjun AU - Chen Z FAU - Miles, John J AU - Miles JJ FAU - Liu, Yu Chih AU - Liu YC FAU - Bell, Melissa J AU - Bell MJ FAU - Sullivan, Lucy C AU - Sullivan LC FAU - Kjer-Nielsen, Lars AU - Kjer-Nielsen L FAU - Brennan, Rebekah M AU - Brennan RM FAU - Burrows, Jacqueline M AU - Burrows JM FAU - Neller, Michelle A AU - Neller MA FAU - Khanna, Rajiv AU - Khanna R FAU - Purcell, Anthony W AU - Purcell AW FAU - Brooks, Andrew G AU - Brooks AG FAU - McCluskey, James AU - McCluskey J FAU - Rossjohn, Jamie AU - Rossjohn J FAU - Burrows, Scott R AU - Burrows SR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100621 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Epitopes) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B*35:01 antigen) RN - 0 (HLA-B35 Antigen) RN - 0 (Peptides) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - *Alleles MH - Amino Acid Sequence MH - Cell Line, Tumor MH - Epitopes/chemistry/genetics MH - HLA-B Antigens/chemistry/genetics MH - HLA-B35 Antigen MH - Humans MH - Immunity/*genetics MH - Models, Molecular MH - Molecular Sequence Data MH - Mutation/genetics MH - Peptides/chemistry/immunology MH - Polymorphism, Single Nucleotide/*genetics MH - Protein Structure, Secondary MH - Receptors, Antigen, T-Cell/chemistry/*genetics MH - Surface Plasmon Resonance PMC - PMC2901058 EDAT- 2010/06/23 06:00 MHDA- 2010/07/31 06:00 PMCR- 2011/01/05 CRDT- 2010/06/23 06:00 PHST- 2010/06/23 06:00 [entrez] PHST- 2010/06/23 06:00 [pubmed] PHST- 2010/07/31 06:00 [medline] PHST- 2011/01/05 00:00 [pmc-release] AID - jem.20100603 [pii] AID - 20100603 [pii] AID - 10.1084/jem.20100603 [doi] PST - ppublish SO - J Exp Med. 2010 Jul 5;207(7):1555-67. doi: 10.1084/jem.20100603. Epub 2010 Jun 21.