Lack of heterologous cross-reactivity toward HLA-A∗02:01 restricted viral epitopes is underpinned by distinct ôôT cell receptor signatures

EJ Grant; TM Josephs; SA Valkenburg; L Wooldridge; M Hellard; J Rossjohn; M Bharadwaj; K Kedzierska; S Gras

Journal article

Lack of heterologous cross-reactivity toward HLA-A∗02:01 restricted viral epitopes is underpinned by distinct ôôT cell receptor signatures

EJ Grant, TM Josephs, SA Valkenburg, L Wooldridge, M Hellard, J Rossjohn, M Bharadwaj, K Kedzierska, S Gras

Journal of Biological Chemistry | ELSEVIER | Published : 2016

DOI: 10.1074/jbc.M116.753988

Abstract

αβT cell receptor (TCR) genetic diversity is outnumbered by the quantity of pathogenic epitopes to be recognized. To provide efficient protective anti-viral immunity, a single TCR ideally needs to cross-react with a multitude of pathogenic epitopes. However, the frequency, extent, and mechanisms of TCR crossreactivity remain unclear, with conflicting results on anti-viral T cell cross-reactivity observed in humans. Namely, both the presence and lack of T cell cross-reactivity have been reported with HLA-A∗02:01-restricted epitopes from the Epstein-Barr and influenza viruses (BMLF-1 and M158 , respectively) or with the hepatitis C and influenza viruses (NS31073 and NA231, respectively). Given..

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University of Melbourne Researchers

Sophie Valkenburg Author

Margaret Hellard Author

Jamie Rossjohn Author

Mandvi Bharadwaj Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

This work was supported by Australian NHMRC Project Grant AI1008854 and Program Grant AI1071916 (to K. K.), an NHMRC Aboriginal and Torres Strait Islander Health Research Scholarship (to E. J. G.), a Douglas and Lola Douglas Scholarship in Medical Science (to E. J. G.), an NHMRC C. J. Martin Fellowship (to E. J. G.), NHMRC Australia Fellowship AF50 (to J. R.), Australian Research Council (ARC) Future Fellowship FF120100416 (to S. G.), and an NHMRC Senior Research Fellow level B (SRFB) Fellowship (to K. K.). The authors declare that they have no conflicts of interest with the contents of this article.