The T lymphocyte response to cytochrome c--II. Molecular characterization of a pigeon cytochrome c determinant recognized by proliferating T lymphocytes of the B10.A mouse.

The T lymphocyte response to cytochrome c--II. Molecular characterization of a pigeon cytochrome c determinant recognized by proliferating T lymphocytes of the B10.A mouse.
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T 淋巴细胞对细胞色素 c--II 的反应。

DOI:
10.1016/0161-5890(80)90030-9
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发表时间:
1980
影响因子:
3.6
通讯作者:
Schwartz,RH
Schwartz,RH
中科院分区:
医学3区
文献类型:
--
作者:
Ultee,ME;Margoliash,E;Lipkowski,A;Flouret,G;Solinger,AM;Lebwohl,D;Matis,LA;Chen,C;Schwartz,RH

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通过检测B10的T淋巴细胞对多种其他物种细胞色素及其溴化氰裂解片段的反应,研究了B10淋巴细胞对鸽细胞色素的增殖反应的分子特异性。用鸽子蛋白免疫小鼠。对应答具有主要影响的氨基酸残基是位于位置100、103和104处的那些。免疫显性抗原残基先前已定位于鸽蛋白的羧基末端区域,并且在当前的研究中通过观察到的对虫和烟草天蛾蛾细胞色素C末端肽片段的反应证实了这种定位。一个意想不到的交叉刺激与金枪鱼cytochromecled的特点,发现丝氨酸可以完全取代的谷氨酰胺在位置100,和第二个cytochromec的发现,从螺旋蠕虫苍蝇,这可能会引起一个heteroclitic T细胞反应。从我们对不同细胞色素c的比较研究中,似乎完全刺激需要在位置100处的不带电残基和在C末端位置103或104处的赖氨酸。然而,其他残基无疑在决定簇的结构中起作用,例如在位置3的空间上接近的异亮氨酸,其被发现负责某些肽片段的刺激活性。我们未能合成一种可以刺激T细胞增殖反应的小肽,凸显了这一点。没有活动被认为是与表面模拟肽或C-末端肽延伸到8个氨基酸的长度和含有的残基确定为免疫显性的决定簇。为了获得抗原性,对大肽的明显需求表明,决定簇的形成需要肽中一定程度的二级或三级结构,或者在分子中存在第二个重要区域,位于残基81和96之间,其可能构成巨噬细胞结合的位点。
The molecular specificity of the 1 lymphocyte proliferative response to pigeon cytochromecwas investigated by testing the response to numerous other species' cytochromescand their cyanogen bromide cleavage fragments by T Ivmnhocytes of B10. A mice immunized to the pigeon protein. Amino acid residues having a major effect on the response were those located at positions 100, 103 and 104. The immunodominant antigenic residues had been previously localized to the carboxyl-terminal region of the pigeon protein, and this localization was confirmed in the current study by the responses seen to the C-terminal peptide fragments of the hippopotamus and tobacco hornworm moth cytochromesc. Characterization of an unexpected cross-stimulation with tuna cytochromecled to the finding that a serine could completely substitute for the glutamine at position 100, and the discovery of a second cytochromec, that from the screw worm fly, that could elicit a heteroclitic T cell response. From our comparative studies with different cytochromesc, it appeared that both an uncharged residue at position 100, and a lysine at the C-terminal position 103 or 104, were required for full stimulation. However, other residues undoubtedly play a role in the structure of the determinant, such as the spatially-close isoleucine at position 3, which was found to be responsible for the stimulatory activity of certain peptide fragments. This point was highlighted by our failure to synthesize a small peptide that could stimulate a T cell proliferative response. No activity was seen with either surface-simulated peptides or C-terminal peptides extending up to eight amino acids in length and containing the residues identified as immunodominant in the determinant. This apparent requirement for a large peptide in order to achieve antigenicity suggests either that formation of the determinant requires some degree of secondary or tertiary structure in the peptide or that a second important region exists in the molecule, located between residues 81 and 96, which perhaps constitutes a site to which the macrophage binds.