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Identifying the immune interactions underlying HLA class I disease associations.

Published version
Peer-reviewed

Type

Article

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Authors

Debebe, Bisrat J 
Boelen, Lies 
Lee, James C 
IAVI Protocol C Investigators 
Sanders, Eduard J 

Abstract

Variation in the risk and severity of many autoimmune diseases, malignancies and infections is strongly associated with polymorphisms at the HLA class I loci. These genetic associations provide a powerful opportunity for understanding the etiology of human disease. HLA class I associations are often interpreted in the light of 'protective' or 'detrimental' CD8+ T cell responses which are restricted by the host HLA class I allotype. However, given the diverse receptors which are bound by HLA class I molecules, alternative interpretations are possible. As well as binding T cell receptors on CD8+ T cells, HLA class I molecules are important ligands for inhibitory and activating killer immunoglobulin-like receptors (KIRs) which are found on natural killer cells and some T cells; for the CD94:NKG2 family of receptors also expressed mainly by NK cells and for leukocyte immunoglobulin-like receptors (LILRs) on myeloid cells. The aim of this study is to develop an immunogenetic approach for identifying and quantifying the relative contribution of different receptor-ligand interactions to a given HLA class I disease association and then to use this approach to investigate the immune interactions underlying HLA class I disease associations in three viral infections: Human T cell Leukemia Virus type 1, Human Immunodeficiency Virus type 1 and Hepatitis C Virus as well as in the inflammatory condition Crohn's disease.

Description

Keywords

CD8 T cell, GWAS, HLA, computational biology, disease association, human, immunogenetics, immunology, inflammation, natural killer cell, systems biology

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications Ltd

Rights

CC0 No rights reserved
Sponsorship
Wellcome Trust (105920/Z/14/Z)
MRC (via University College London (UCL)) (15012)