HLA-C and HIV-1: friends or foes?

• Main Authors: Zipeto Donato, Beretta Alberto
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: Retrovirology
• Subjects: MHC class I; HLA-C; Open conformers; HIV-1; CTL; NK cells; KIR; β₂₋microglobulin
• Online Access: http://www.retrovirology.com/content/9/1/39

<p>Abstract</p> <p>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.</p>