title: HLA-C and HIV-1: friends or foes?
abstract: The major histocompatibility complex class I protein HLA-C plays a crucial role as a molecule capable of sending inhibitory signals to both natural killer (NK) cells and cytotoxic T lymphocytes (CTL) via binding to killer cell Ig-like receptors (KIR). Recently HLA-C has been recognized as a key molecule in the immune control of HIV-1. Expression of HLA-C is modulated by a microRNA binding site. HLA-C alleles that bear substitutions in the microRNA binding site are more expressed at the cell surface and associated with the control of HIV-1 viral load, suggesting a role of HLA-C in the presentation of antigenic peptides to CTLs. This review highlights the role of HLA-C in association with HIV-1 viral load, but also addresses the contradiction of the association between high cell surface expression of an inhibitory molecule and strong cell-mediated immunity. To explore additional mechanisms of control of HIV-1 replication by HLA-C, we address specific features of the molecule, like its tendency to be expressed as open conformer upon cell activation, which endows it with a unique capacity to associate with other cell surface molecules as well as with HIV-1 proteins.
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Zipeto
authors.forename: Alberto
authors.initials: A
authors.lastname: Beretta
mesh_terms: D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D012323:RNA Processing, Post-Transcriptional; D014779:Virus Replication / Q000276:immunology
chemical_list: D015236:HLA-C Antigens