ALLELE-SPECIFIC CONTROL OF IA MOLECULE SURFACE EXPRESSION AND CONFORMATION - IMPLICATIONS FOR A GENERAL-MODEL OF IA STRUCTURE-FUNCTION-RELATIONSHIPS

ALLELE-SPECIFIC CONTROL OF IA MOLECULE SURFACE EXPRESSION AND CONFORMATION - IMPLICATIONS FOR A GENERAL-MODEL OF IA STRUCTURE-FUNCTION-RELATIONSHIPS
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DOI:
10.1073/pnas.84.9.2921
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发表时间:
1987-05-01
影响因子:
11.1
通讯作者:
GERMAIN, RN
GERMAIN, RN
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BRAUNSTEIN, NS;GERMAIN, RN

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II类主要组织相容性复合体编码分子(Ia)的序列多态性不仅解释了与t淋巴细胞反应相关的Ia结构的等位基因变异,而且似乎导致了特定Ia异源二聚体的差异定量表达。通过转染不同的a. β细胞,分析了Ia分子的不同等位变异区域对这两个过程的贡献。和A.alpha。基因对。结果表明,在Ia表达的定量和定性方面,a. β。链条分成两组。这些在a. β的nh2末端。我一直在控制β - α。链相互作用,二聚体表达效率和Ia构象,并且可能位于Ia分子内部的。β。-。α位点。域交互。a. β的cooh末端的多态性。1参与那些直接与抗体、抗原和/或t细胞受体相互作用的结构,与它们在Ia异源二聚体表面的存在一致。这一分析为理解II类分子的整体结构以及这种结构与免疫识别之间的关系提供了一个模型。这也为II类基因的某些特征的进化提供了一种解释。
Sequence polymorphism of class II major histocompatibility complex-encoded molecules (Ia) not only accounts for the allelic variability in Ia structure relevant to T-lymphocyte responses but also seems to result in differential quantitative expression of particular Ia heterodimers. The contributions of different allelically variable regions of Ia molecules to both of these processes were analyzed by transfection of L cells with various A.beta. and A.alpha. gene pairs. The results show that, with regard to quantitative and qualitative aspects of Ia expression, the polymorphisms in the A.beta. chain segregate into two groups. Those in the NH2-terminal half of A.beta.1 have a consistent role in controlling .beta.-.alpha. chain interactions, efficiency of dimer expression, and Ia conformation and probably are in the interior of the Ia molecule at the site of .beta.-.alpha. domain interaction. Polymorphisms in the COOH-terminal half of A.beta.1 contribute to those structures that directly interact with antibodies, antigen, and/or T-cell receptors, consistent with their presence on the surface of the Ia heterodimer. This analysis provides a model for understanding both overall class II molecular structure and the relationship between this structure and immune recognition. It also suggests an explantation for the evolution of certain features of class II genes.