Published in
Rockefeller University Press, Journal of Experimental Medicine, 1(206), p. 209-219, 2009
DOI: 10.1084/jem.20082136
Links
- Rockefeller University Press | PDF
- ORCID
- ORCID
- [www.ncbi.nlm.nih.gov] | PDF
- [espace.library.uq.edu.au]
- [arrow.monash.edu.au]
- [espace.library.uq.edu.au] | PDF
- [europepmc.org] | PDF
- [www.researchgate.net]
- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [researchonline.jcu.edu.au] | PDF
Tools
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition
,
Melissa J. Bell,
Rebekah M. Brennan,
Travis Clarke Beddoe,
Matthew Charles James Wilce,
Craig Steven Clements,
Anthony W. Purcell ,
James McCluskey,
Scott R. Burrows,
Jamie Rossjohn
Full text: Download
Abstract
Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell-mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR-HLA-B*4405(EENLLDFVRF) complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.