MICA polymorphism: biology and importance in immunity and disease

Abstract

The human major histocompatibility complex class I chain-related gene A (MICA) is one of the genes in the HLA class I region of chromosome 6. Unlike HLA classical class I gene products, MICA does not present any antigen but acts as a ligand for several immune cells including natural killer (NK) cells bearing NKG2D receptors. MICA is the member of the non-classical class I family that displays the greatest degree of polymorphism. MICA alleles can be divided into two large groups with the polymorphisms found in alpha3 domains. This division could be explained by a possible polyphyletic origin that is in line with recent findings from evolutionary, population and functional studies of this gene. MICA polymorphisms are associated with a number of diseases related to NK activity, such as viral infection, cancer and allograft rejection or graft-versus-host disease (GVHD). The mechanisms underlying these associations include NK cell-mediated cytotoxicity and MICA shedding to produce immunosuppressive soluble MICA particles. The MICA-induced humoral response has attracted interest recently because of its possible role in graft rejection in solid organ transplantation. Here, we discuss the genetics and biology of the MICA gene and its products, and their importance in disease.