Identifying the immune interactions underlying HLA class I disease associations

Journal article

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.

Authors: Debebe, BJ; Boelen, L; Lee, JC; Sanders, EJ; Anzala, O

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: eLife Sciences Publications
• Journal: eLife
• Volume: 9
• Article number: e54558
• Publication date: 2020-05-27
• Acceptance date: 2020-03-06
• DOI: 10.7554/elife.54558
• EISSN: 2050-084X
• Pmid: 32238263
• Language: English
• Keywords: IAVI Protocol C Investigators; FFR