title: The multi-faceted nature of HLA class I dimer molecules.
abstract: The canonical role of major histocompatibility complex class I (MHCI) molecules in antigen presentation involves the recognition of a short peptide of intracellular origin, bound to the upper surface of the class I molecule, by CD8(+) T lymphocytes. Assembly and loading of the MHCI is a highly regulated, chaperone-mediated process and only when the fully folded MHCI molecule is correctly loaded with peptide is it released from the endoplasmic reticulum for trafficking to the cell surface. Current models of the interactions of MHCI molecules with their cognate receptors visualize them functioning as monomeric entities. However, in recent years, new data have revealed MHCI molecules with the ability to form disulphide-linked dimeric structures, with several distinct dimer entities being elucidated. We describe here three types of MHCI dimers; HLA-B27 dimers formed predominantly through the possession of an unpaired cysteine within the peptide-binding groove; HLA-G dimers, which form through a cysteine on its external surface; and a novel population we term redox-induced dimers, which can form between cysteine residues in the cytoplasmic tail domains. The characteristics of these dimeric MHCI molecules and their role in both normal immune responses and in disease pathogenesis are reviewed in this article.
authors.affiliation: School of Medicine, University of St Andrews, Fife, UK.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Campbell
authors.forename: Antony N
authors.initials: AN
authors.lastname: Antoniou
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Powis
mesh_terms: D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005805:Genes, MHC Class I; D015796:HLA-B27 Antigen / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D059951:HLA-G Antigens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D055503:Protein Multimerization
chemical_list: D015796:HLA-B27 Antigen; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I