Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Box 110, Level 6, Addenbrooke's Centre for Clinical Investigation (ACCI), Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Trends Mol Med. 2010 Mar;16(3):97-106. doi: 10.1016/j.molmed.2010.01.002. Epub 2010 Feb 12.
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.
人类主要组织相容性复合体Ⅰ类链相关基因 A（MICA）是染色体 6 号 HLA Ⅰ类区域的基因之一。与 HLA 经典Ⅰ类基因产物不同，MICA 不呈递任何抗原，而是作为包括携带 NKG2D 受体的自然杀伤 (NK) 细胞在内的几种免疫细胞的配体。MICA 是具有最大多态性的非经典Ⅰ类家族的成员。MICA 等位基因可分为两个大组，其多态性存在于α3 结构域中。这种划分可以通过可能的多系起源来解释，这与该基因的进化、群体和功能研究的最新发现一致。MICA 多态性与许多与 NK 活性相关的疾病有关，例如病毒感染、癌症和同种异体移植排斥或移植物抗宿主病 (GVHD)。这些关联的机制包括 NK 细胞介导的细胞毒性和 MICA 脱落产生免疫抑制性可溶性 MICA 颗粒。由于其在实体器官移植中排斥移植物的可能作用，MICA 诱导的体液反应最近引起了关注。在这里，我们讨论了 MICA 基因及其产物的遗传学和生物学，以及它们在疾病中的重要性。
