Year: 2020
Type: article
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.
Source: eLife
DOI: 10.7554/elife.54558
Authors: Bisrat J Debebe, Lies Boelen, James C Lee, IAVI Protocol C Investigators, Eduard J Sanders, Omu Anzala, Anatoli Kamali, Pontiano Kaleebu, Etienne Karita, William Kilembe, Mubiana Inambao, Shabir Lakhi, Susan Allen, Eric Hunter, Vinodh A Edward, Pat E Fast, Matt A Price, Jill Gilmour, Jianming Tang, Chloe L Thio, Jacquie Astemborski, Gregory Kirk, Salim I Khakoo, Sharyne M Donfield, James J Goedert, Becca Asquith
Institutions: Imperial College London, University of Cambridge, Kenya Medical Research Institute, University of Oxford, KEMRI-Wellcome Trust Research Programme, Kenya AIDS Vaccine Initiative, International AIDS Vaccine Initiative, MRC/UVRI & LSHTM Uganda Research Unit, Medical Research Council, Uganda Virus Research Institute, Emory University, Aurum Institute, University of California, San Francisco, University of Alabama, University of Alabama at Birmingham, Johns Hopkins University, University of Southampton, Rho (United States), National Cancer Institute, Division of Cancer Epidemiology and Genetics
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: U.S. Department of Health and Human Services, United States Agency for International Development, International AIDS Vaccine Initiative, Leukemia and Lymphoma Research, Wellcome Trust, European Commission, Bloodwise, Blood Cancer UK, National Institutes of Health, Seventh Framework Programme, Medical Research Council, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Patient-Oriented Research and Mentorship in HIV and Non-Communicable Diseases, INCIDENCE OF HIV INFECTION IN A COHORT OF IV DRUG USERS, G246226756, G2668872129, G2971608318, G3048292517, Quantitative T cell Immunology, G3432529795, G3450022006, G3630728887, Inhibitory KIRs and virus-specific adaptive immunity in humans., G6696627941, Pathogenesis of HIV and HCV in Hemophilia: HGDS, G7856892013, Long non-coding RNAs in immunity and disease pathogenesis., G789740612, G9000102917, G9000118633, G9000326663, AIDS Linked to the IntraVenous Experience (ALIVE) Study
OpenAlex ID: W3014295077