Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C.
Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C.
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DOI：
10.1084/jem.176.4.937
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发表时间：
1992-10-01
影响因子：
15.3
通讯作者：
PARHAM, P
中科院分区：
文献类型：
--
作者：
ZEMMOUR, J;PARHAM, P
HLA-C位点仍然是一个谜。血清学多态性定义不明确，HLA-C分子在细胞表面的表达水平约为HLA-A和-B的10%，它们对抗原呈递给携带CD 8的T细胞或自然杀伤细胞的重要性尚不清楚。我们对HLA-C多态性的理解也落后于HLA-A和-B。我们应用聚合酶链反应的cDNA编码HLA-C抗原的特性。将最近的结果与先前表征的HLA-C等位基因相结合，得到了26个序列的数据库，该数据库用于分析HLA-C多态性的性质，并将其与HLA-A和-B中所见的变异进行比较。这些序列形成了10个等位基因家族，与血清学交叉反应性模式（包括C空白）密切相关，所有主要的HLA-C等位基因家族似乎都已取样。这些家族进一步分为两组HLA-C等位基因，其根据3'外显子中的连锁取代来定义。与HLA-A和-B相比，HLA-C等位基因彼此之间的关系更密切，在抗原识别位点的残基上存在较少的变异，而在其它位置上存在较多的变异。特别地，HLA-C分子的α 1结构域的螺旋是异常保守的。尽管抗原识别位点的多样性降低，但很明显HLA-C基因一直是过去选择多态性的目标。在抗原识别位点内，α 1结构域是HLA-C最具诊断性的，而α 2结构域与HLA-B的结构域相似，HLA-B是与HLA-C最密切相关的基因座。特别地，α 1螺旋中的保守基序和B口袋（位置45）的碱基处的保守甘氨酸提供了在HLA-C分子中唯一发现的特征的组合。我们假设这些特征限制了HLA-C分子结合的肽，并以这种方式降低了HLA-C在细胞表面组装和表达的效率。从该HLA-C等位基因取样获得的HLA-C多态性的总体情况不太可能随着进一步的等位基因的表征而改变。
The HLA-C locus remains an enigma. The serological polymorphism is poorly defined, HLA-C molecules are expressed at the cell surface at about 10% the levels of HLA-A and -B, and their importance for antigen presentation to either CD8-bearing T cells or natural killer cells is unclear. Our understanding of HLA-C polymorphism has also lagged behind that of HLA-A and -B. We have applied the polymerase chain reaction to the characterization of cDNA encoding HLA-C antigens. Combining the recent results with previously characterized HLA-C alleles gives a data base of 26 sequences, which was used to analyze the nature of HLA-C polymorphism and compare it to the variation seen in HLA-A and -B. The sequences form 10 families of alleles that correlate well with the patterns of serological crossreactivity, including the C blanks, and all major HLA-C allelic families appear to have been sampled. The families further divide into two groups of HLA-C alleles defined on the basis of linked substitutions in the 3' exons. In comparison with HLA-A and -B, HLA-C alleles are more closely related to each other, there being less variation in residues of the antigen recognition site and more variation at other positions. In particular, the helix of the alpha 1 domain of HLA-C molecules is unusually conserved. Despite the reduced diversity in the antigen recognition site, it is evident that HLA-C genes have been the target of past selection for polymorphism. Within the antigen recognition site, it is the alpha 1 domain that is most diagnostic of HLA-C, whereas the alpha 2 domain is similar to that of HLA-B, the locus to which HLA-C is most closely related. In particular, conserved motifs in the alpha 1 helix and the conserved glycine at the base of the B pocket (position 45) provide a combination of features that is uniquely found in HLA-C molecules. We hypothesize that these features restrict the peptides bound by HLA-C molecules and in this manner reduce the efficiency of HLA-C assembly and expression at the cell surface. The overall picture HLA-C polymorphism obtained from this sampling of HLA-C alleles is unlikely to change as further alleles are characterized.
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影响因子：
5.4
作者：
BERETTA, A;GRASSI, F;SICCARDI, AG
通讯作者：
SICCARDI, AG
影响因子：
--
作者：
BODMER, JG;MARSH, SGE;TERASAKI, PI
通讯作者：
TERASAKI, PI
影响因子：
64.8
作者：
BELICH, MP;MADRIGAL, JA;PARHAM, P
通讯作者：
PARHAM, P
影响因子：
2.7
作者：
CHEN, BP;LAM, V;SONDEL, PM
通讯作者：
SONDEL, PM
DOI：
10.1083/jcb.112.6.1099
发表时间：
1991-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Degen E;Williams DB
通讯作者：
Williams DB