The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens.
The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens.
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DOI：
10.1084/jem.142.6.1349
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发表时间：
1975-12-01
期刊：
影响因子：
--
通讯作者：
Bevan MJ
中科院分区：
文献类型：
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作者：
Bevan MJ
通过用来自携带相同H-2区的同种异体品系的细胞免疫一个品系的小鼠来产生细胞毒性细胞。在4小时51铬释放试验中测定的效应细胞被证明是T细胞和不可区分的，除了在特异性，细胞毒性T细胞针对H-2同种异体抗原。虽然负责免疫的应答细胞和刺激细胞之间的遗传差异没有编码H-2，但H-2复合物确实限制了靶细胞的易感性。例如，针对C57 BL/6细胞（H-2 B）免疫并能够裂解C57 BL/6细胞（H-2 B）的BALB.B细胞毒性细胞（H-2 b）不会裂解B6. C/H-2 d靶细胞。C57 BL/6和B6.C/H-2d是同源的，并且在H-2区不同。两种假设被认为是解释H-2限制的敏感性细胞毒性T细胞产生的H-2相同的同种异体免疫。(a)双重（自我）识别假说指出，细胞毒性细胞有两个识别单位，一个是H-2编码的结构，另一个是次要同种异体抗原的克隆限制性受体。(b)相互作用抗原假说认为，细胞毒性T细胞识别的所有表面同种抗原决定簇都是H-2和非H-2编码基因产物相互作用的结果。两条线的证据，一个与F1效应细胞和其他冷靶竞争实验，提出了强烈主张赞成的相互作用抗原假说。H-2需要组织相容性的区域被映射到D区和IC的左侧，可能是K区。这些结果，以及最近对病毒感染和TNP修饰的同基因细胞的反应的研究表明，细胞毒性细胞在特异性上受到限制，优先识别编码在主要组织相容性复合体中的结构改变。
Cytotoxic cells were generated by immunizing one strain of mouse with cells from an allogeneic strain which carries the same H-2 region. The effector cells assayed in a 4 h 51Cr release assay were shown to be T cells and indistinguishable, except in specificity, from cytotoxic T cells directed at H-2 alloantigens. Although the genetic differences between responder and stimulator cells responsible for the immunization did not code in H-2, the H-2 complex did restrict susceptibility of target cells. For example, BALB.B cytotoxic cells (H-2b) immunized against and capable of lysing C57BL/6 cells (H-2b) would not lyse B6.C/H-2d target cells. C57BL/6 and B6.C/H-2d are congenic and differ in the H-2 region. Two hypotheses are considered to explain the H-2 restriction of susceptibility to cytotoxic T cells generated by an H-2 identical alloimmunization. (a) The dual (self) recognition hypothesis states that the cytotoxic cell has two recognition units, one for H-2- coded structures and another clonally restricted receptor for the minor alloantigen. (b) The interaction antigen hypothesis states that all the surface alloantigenic determinants recognized by cytotoxic T cells are the result of interaction between H-2- and non-H-2-coded gene products. Two lines of evidence, one with F1 effector cells and the other a cold target competition experiment, are presented which argue strongly in favor of the interaction antigen hypothesis. The regions of H-2 required to be histocompatible were mapped to the D region and to the left of IC, probably the K region. These results, and recent work on the response to virus-infected and TNP-modified syngeneic cells, suggest that cytotoxic cells are restricted in specificity to preferentially recognizing alterations in structures that are coded in the major histocompatibility complex.