Allelic polymorphism in the T cell receptor and its impact on immune responses

Gras, Stephanie, Chen, Zhenjun, Miles, John J., Liu, Yu Chih, Bell, Melissa J., Sullivan, Lucy C., Kjer-Nielsen, Lars, Brennan, Rebekah M., Burrows, Jacqueline M., Neller, Michelle A., Khanna, Rajiv, Purcell, Anthony W., Brooks, Andrew G., McCluskey, James, Rossjohn, Jamie, and Burrows, Scott R. (2010) Allelic polymorphism in the T cell receptor and its impact on immune responses. The Journal of Experimental Medicine, 207 (7). pp. 1555-1567.

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Abstract

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 CDR2β 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*3501HPVGEADYFEY 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.

Item ID: 45238
Item Type: Article (Research - C1)
ISSN: 1540-9538
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© 2010 Gras et al.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

Funders: Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC)
Date Deposited: 06 Sep 2016 05:02
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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