Diversification, expression, and gamma delta T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules.
Diversification, expression, and gamma delta T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules.
复制标题
主要组织相容性复合物 I 类相关分子的 MIC 家族进化上较远的成员的多样化、表达和 γ δ T 细胞识别。
DOI：
10.1073/pnas.95.21.12510
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发表时间：
1998
影响因子：
11.1
通讯作者：
Spies,T
中科院分区：
文献类型：
--
作者：
Steinle,A;Groh,V;Spies,T
主要组织相容性复合体I类分子的远亲人类MICA和MICB是应激诱导的抗原，被肠道上皮γδT细胞广泛识别。因此，它们可能在受损、感染或应激的肠道上皮细胞的免疫监测中发挥核心作用。然而，该系统在进化过程中的共性以及对MICA和MICB的识别模式尚不明确。对不同灵长类物种的cdna序列分析确定了与MICA和MICB同源的翻译产物。所有的MIC多肽都有共同的特征，尽管它们非常不同。最显著的变化是在α-螺旋区的α1α2结构域的几个缺失和频繁的氨基酸替换。而灵长类MIC分子在正常细胞和转基因细胞表面均有表达。此外，尽管它们在α1α2结构域的潜在可及区域有相对较少的相同氨基酸，但它们被不同的人肠道上皮γδT细胞识别，这些T细胞受到MICA和MICB的限制。因此，MIC分子代表了一类结构多样但似乎功能保守的MHC蛋白家族。γδT细胞对这些抗原的杂乱识别模式可能是因为它们共享一个保守的相互作用位点。
Distant relatives of major histocompatibility complex (MHC) class I molecules, human MICA and MICB, function as stress-induced antigens that are broadly recognized by intestinal epithelial γδ T cells. They may thus play a central role in the immune surveillance of damaged, infected, or otherwise stressed intestinal epithelial cells. However, the generality of this system in evolution and the mode of recognition of MICA and MICB are undefined. Analysis of cDNA sequences from various primate species defined translation products that are homologous to MICA and MICB. All of the MIC polypeptides have common characteristics, although they are extraordinarily diverse. The most notable alterations are several deletions and frequent amino acid substitutions in the putative α-helical regions of the α1α2domains. However, the primate MIC molecules were expressed on the surfaces of normal and transfected cells. Moreover, despite their sharing of relatively few identical amino acids in potentially accessible regions of their α1α2domains, they were recognized by diverse human intestinal epithelial γδ T cells that are restricted by MICA and MICB. Thus, MIC molecules represent a family of MHC proteins that are structurally diverse yet appear to be functionally conserved. The promiscuous mode of γδ T cell recognition of these antigens may be explained by their sharing of a single conserved interaction site.