A molecular basis for the interplay between T cells, viral mutants, and human leukocyte antigen micropolymorphism

Liu, Yu Chih, Chen, Zhenjun, Neller, Michelle A., Miles, John J., Purcell, Anthony W., McCluskey, James, Burrows, Scott R., Rossjohn, Jamie, and Gras, Stephanie (2014) A molecular basis for the interplay between T cells, viral mutants, and human leukocyte antigen micropolymorphism. Journal of Biological Chemistry, 289 (24). pp. 16688-16698.

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Abstract

Mutations within T cell epitopes represent a common mechanism of viral escape from the host protective immune response. The diverse T cell repertoire and the extensive human leukocyte antigen (HLA) polymorphism across populations is the evolutionary response to viral mutation. However, the molecular basis underpinning the interplay between HLA polymorphism, the T cell repertoire, and viral escape is unclear. Here we investigate the T cell response to a HLA-B*35:01- and HLA-B*35:08-restricted (⁴⁰⁷)HPVGEADYFEY(⁴¹⁷) epitope from Epstein-Barr virus and naturally occurring variants at positions 4 and 5 thereof. Each viral variant differently impacted on the epitope's flexibility and conformation when bound to HLA-B*35:08 or HLA-B*35:01. We provide a molecular basis for understanding how the single residue polymorphism that discriminates between HLA-B*35:01/08 profoundly impacts on T cell receptor recognition. Surprisingly, one viral variant (P5-Glu to P5-Asp) effectively changed restriction preference from HLA-B*35:01 to HLA-B*35:08. Collectively, our study portrays the interplay between the T cell response, viral escape, and HLA polymorphism, whereby HLA polymorphism enables altered presentation of epitopes from different strains of Epstein-Barr virus.

Item ID: 45058
Item Type: Article (Research - C1)
ISSN: 1083-351X
Funders: Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC APP1067374, NHMRC APP1021620
Date Deposited: 09 Aug 2016 04:58
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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