Natural Micropolymorphism in Human Leukocyte Antigens Provides a Basis for Genetic Control of Antigen Recognition

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2009 Jan 14

PMID 19139173

Citations 51

Authors

Julia K Archbold

Whitney A Macdonald

Stephanie Gras

Lauren K Ely

John J Miles

Melissa J Bell

Rebekah M Brennan

Travis Beddoe

Matthew C J Wilce

Craig S Clements

Anthony W Purcell

James McCluskey

Scott R Burrows

Jamie Rossjohn

Affiliations

Soon will be listed here.

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.

Citing Articles

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HLA Class I (A and B) Allele Polymorphism in a Moroccan Population Infected with Hepatitis C Virus.

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