PROTEOLYSIS OF THE HEAVY-CHAIN OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ANTIGENS BY COMPLEMENT COMPONENT-C1S
PROTEOLYSIS OF THE HEAVY-CHAIN OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ANTIGENS BY COMPLEMENT COMPONENT-C1S
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DOI：
10.1016/0167-4838(90)90169-g
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发表时间：
1990-02-09
期刊：
影响因子：
--
通讯作者：
NISSEN, MH
中科院分区：
文献类型：
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作者：
ERIKSSON, H;NISSEN, MH
主要组织相容性复合体（MHC）I类抗原含有轻链β 2-微球蛋白，其与transmemorane heary α-微球蛋白非共价结合。携带同种异型决定簇的链。由于已知C1 g补体成分与β 2-微球蛋白相关，并且我们最近发现激活的C1 s补体能够切割β 2-微球蛋白，因此我们决定研究C1补体对I类抗原重链的蛋白水解活性。我们的研究结果表明，人C1 s补体切割成至少两个片段，与表观分子量为22000和24000 gmol的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE），在还原和非还原条件下的人I类抗原的重链。C1酯酶抑制剂可抑制重链裂解。片段的分子量与位于重链α 2-和α 3-结构域的二硫环之间区域的裂解一致。此外，人C1 s补体能够以类似的方式切割来自小鼠的H-2抗原，但不能切割大鼠MHC I类抗原或小鼠MHC II类抗原（I-Ad）。C1 r和C1 s孵育的小鼠脾上清中也可检测到小鼠MHC I类抗原特异性决定簇。这些结果表明在体液中存在非膜结合的可溶形式的α 1-和α 2-结构域，其代表抗原肽的结合位点。
The major histocompatibility complex (MHC) class I antigens contain a light chain, .beta.2-microglobulin, non-covalently associated to the transmemorane heary .alpha.-chain carrying the allotypic determinants. Since the C1g complement component is known to associate with .beta.2-microglobulin, and we recently found that activated C1s complement was capable of cleaving .beta.2-microglobulin, we decided to investigate the proteolytic activity of C1 complement towards the heavy chain of class I antigens. Our results demonstrate that human C1s complement cleaves the heavy chain of human class I antigens into at least two fragments, with apparent molecular weights of 22000 and 24000 gmol on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), under both reducing and non-reducing conditions. The cleavage of the heavy chain is inhibited by the presence of C1 esterase inhibitor. The molecular weights of the fragments are in agreement with the cleavage located in the area between the disulphide loops of the .alpha.2-and .alpha.3-domains of the heavy chain. In addition human C1s complement is able to cleave H-2 antigens from mouse in a similar fashion but not rat MHC class I antigen or mouse MHC class II antigen (I-Ad). Mouse MHC class I antigen-specific determinants could also be detected in supernant from mouse spleen incubated with C1r and C1s. These results indicate the presence in the body fluids of a non-membrane-bound soluble form of the .alpha.1- and .alpha.2-domains which represent the binding site for antigenic peptides.