Journal article
Allelic polymorphism in the T cell receptor and its impact on immune responses
S Gras, Z Chen, JJ Miles, YC Liu, MJ Bell, LC Sullivan, L Kjer-Nielsen, RM Brennan, JM Burrows, MA Neller, R Khanna, AW Purcell, AG Brooks, J McCluskey, J Rossjohn, SR Burrows
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2010
DOI: 10.1084/jem.20100603
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..
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Funding Acknowledgements
This work was supported by the Australian Research Council (ARC; Federation Fellowship to J. Rossjohn) and the National Health and Medical Research Council (NHMRC) of Australia (Career Development Award to L.C. Sullivan; Senior Research Fellowships to S.R. Burrows, A.W. Purcell, and R. Khanna; C.J. Martin Overseas Biomedical Fellowship to J.J. Miles; and Dora Lush Scholarship to R.M. Brennan), and by grants from the NHMRC and ARC.