A 2ND LINEAGE OF MAMMALIAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES
A 2ND LINEAGE OF MAMMALIAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES
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DOI：
10.1073/pnas.91.14.6259
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发表时间：
1994-07-05
影响因子：
11.1
通讯作者：
SPIES, T
中科院分区：
文献类型：
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作者：
BAHRAM, S;BRESNAHAN, M;SPIES, T
主要组织相容性复合体（MHC）I类基因通常编码多态性肽结合链，其广泛表达并介导细胞毒性T细胞对细胞内抗原的识别。它们在不同物种中构成了不同的基因家族，包括小鼠H-2复合体中的许多所谓的非经典基因，其中一些基因已经适应了不同的功能。我们已经确定了一个独特的家庭的五个相关序列在人类MHC的远同源的I类链。这些MIC基因（MHC I类链相关基因）与人类I类基因以及大多数哺乳动物（如果不是全部的话）的基因平行进化。该家族中的云母基因位于HLA-B附近，并且是迄今为止已知的最不同的哺乳动物MHC I类基因。它还通过其不寻常的外显子-内含子组织和在成纤维细胞和上皮细胞中的优先表达而进一步区分。然而，在从cDNA翻译的云母氨基酸序列中存在诊断残基表明推定的云母链与典型的I类链类似地折叠，并且可能具有结合肽或其他短配体的能力。这些结果定义了进化上保守的MHC I类基因的第二谱系。这意味着云母和该家族中可能的其他成员已被选择用于专门的功能，这些功能要么是古老的，要么来自典型的MHC I类基因，类似于一些非经典的小鼠H-2基因。
Major histocompatibility complex (MHC) class I genes typically encode polymorphic peptide-binding chains which are ubiquitously expressed and mediate the recognition of intracellular antigens by cytotoxic T cells. They constitute diverse gene families in different species and include the numerous so-called nonclassical genes in the mouse H-2 complex, of which some have been adapted to variously modified functions. We have identified a distinct family of five related sequences in the human MHC which are distantly homologous to class I chains. These MIC genes (MHC class I chain related genes) evolved in parallel with the human class I genes and with those of most if not all mammalian orders. The MICA gene in this family is located near HLA-B and is by far the most divergent mammalian MHC class I gene known. It is further distinguished by its unusual exon-intron organization and preferential expression in fibroblasts and epithelial cells. However, the presence of diagnostic residues in the MICA amino acid sequence translated from cDNA suggests that the putative MICA chain folds similarly to typical class I chains and may have the capacity to bind peptide or other short ligands. These results define a second lineage of evolutionarily conserved MHC class I genes. This implies that MICA and possibly other members in this family have been selected for specialized functions that are either ancient or derived from those of typical MHC class I genes, in analogy to some of the nonclassical mouse H-2 genes.