Identifying the immune interactions underlying HLA class I disease associations

Academic Article


  • Variation in the risk and severity of many autoimmune diseases, malignancies and infections is strongly associated with polymorphisms in 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.
  • Published In

  • eLife  Journal
  • Digital Object Identifier (doi)

    Author List

  • Debebe BJ; Boelen L; Lee JC; Thio CL; Astemborski J; Kirk G; Khakoo SI; Donfield SM; Goedert JJ; Asquith B
  • Volume

  • 9