PEPTIDE VARIANTS REVEAL HOW ANTIBODIES RECOGNIZE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I
PEPTIDE VARIANTS REVEAL HOW ANTIBODIES RECOGNIZE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I
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DOI：
10.1002/eji.1830231145
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发表时间：
1993-11-01
影响因子：
5.4
通讯作者：
BEVAN, MJ
中科院分区：
文献类型：
--
作者：
HOGQUIST, KA;GRANDEA, AG;BEVAN, MJ
CD 8（+）T淋巴细胞上的T细胞受体（TcR）识别由主要组织相容性复合物（MHC）重链、β 2-微球蛋白（β 2 M）和抗原呈递细胞表面的肽组成的复合物。突变分析表明TcR识别重链的α 1和α 2结构域以及肽。最近的研究表明，识别K-b MHC复合物的抗体对结合在沟中的肽是敏感的。我们已经将该分析扩展到包括八种K-b特异性抗体，其中七种是肽敏感的。这些抗体都是同种抗体，它们识别携带K-b的细胞，现在可以理解，这些细胞在其凹槽中具有高度异质的自身肽混合物。我们发现，这些自身肽也可以影响抗体的结合，它已被建议，肽改变的α 1和α 2结构域的重链的构象，这反过来又影响K-b抗体的识别。另一种假设是暴露于溶剂的肽侧链可以阻止抗体结合复合物。使用一组128个单氨基酸的变体的K-b结合抗原肽从卵清蛋白，我们表明，对于大多数K-b特异性抗体，第二个想法是更有可能的。阻止抗体结合的那些变体位于溶剂暴露的位置，并且通常，侧链越大，抗体结合的抑制越大。然而，在两种抗体100.30和34.4.20的情况下，影响抗体识别的肽残基被掩埋，表明这些抗体看到肽/MHC复合物的替代构象。
The T cell receptor (TcR) on CD8(+) T lymphocytes recognizes a complex which consists of a major histocompatibility complex (MHC) heavy chain, beta 2-microglobulin (beta(2)M), and peptide on the surface of antigen-presenting cells. Mutational analyses have suggested that the TcR recognizes both the alpha 1 and alpha 2 domains of the heavy chain as well as the peptide. In light of this, it is of interest to know to what extent the heavy chain domains take on distinct conformations when bound to individual peptides.It has recently been shown that antibodies which recognize the K-b MHC complex are sensitive to which peptides are bound in the groove. We have extended this analysis to include eight K-b-specific antibodies, seven of which are peptide sensitive. These antibodies, all of which are allo-antibodies, recognize K-b-bearing cells which, it is now appreciated, have a highly heterogeneous mix of self peptides presented in their grooves. We show that these self peptides also can affect antibody binding.It has been suggested that peptides alter the conformation of the alpha 1 and alpha 2 domains of the heavy chain and that this in turn affects the recognition of K-b by antibody. An alternative hypothesis is that solvent-exposed peptide side chains may prevent the antibody from binding the complex. Using a panel of 128 single-amino acid variants of a K-b-binding antigenic peptide from ovalbumin we show that for most K-b-specific antibodies, the second idea is more likely. Those variants which prevent antibody binding are at solvent exposed positions, and in general, the bulkier the side chain, the greater the inhibition of antibody binding. However, in the case of two antibodies, 100.30 and 34.4.20, the peptide residues which affect antibody recognition are buried, suggesting that these antibodies see an alternate conformation of the peptide/MHC complex.