The Shaping of T Cell Receptor Recognition by Self-Tolerance

S Gras; SR Burrows; L Kjer-Nielsen; CS Clements; YC Liu; LC Sullivan; MJ Bell; AG Brooks; AW Purcell; J McCluskey; J Rossjohn

Journal article

The Shaping of T Cell Receptor Recognition by Self-Tolerance

S Gras, SR Burrows, L Kjer-Nielsen, CS Clements, YC Liu, LC Sullivan, MJ Bell, AG Brooks, AW Purcell, J McCluskey, J Rossjohn

Immunity | CELL PRESS | Published : 2009

DOI: 10.1016/j.immuni.2008.11.011

Abstract

During selection of the T cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward a trans-HLA (human leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, ..

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University of Melbourne Researchers

Lucy Sullivan Author

Andrew Brooks Author

McCluskey James Author

Jamie Rossjohn Author

Grants

Funding Acknowledgements

We thank the staff at the Australian synchrotron for assistance with data collection. The National Health and Medical Research Council (NHMRC) of Australia, Roche Organ Transplantation Research Foundation, and the Australian Research Council (ARC) supported this research. S.R.B. and A.W.P. are supported by NHMRC Senior Research Fellowships, and J.R. is supported by an ARC Federation Fellowship.