PEPTIDE-DEPENDENT RECOGNITION OF H-2KB BY ALLOREACTIVE CYTO-TOXIC LYMPHOCYTES-T
PEPTIDE-DEPENDENT RECOGNITION OF H-2KB BY ALLOREACTIVE CYTO-TOXIC LYMPHOCYTES-T
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DOI：
10.1038/341749a0
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发表时间：
1989-10-26
期刊：
影响因子：
64.8
通讯作者：
SHERMAN, LA
中科院分区：
文献类型：
--
作者：
HEATH, WR;HURD, ME;SHERMAN, LA
抗原特异性T淋巴细胞似乎识别外来抗原，其形式为主要组织相容性复合体(MHC)编码的I类或II类分子的抗原结合沟内的多肽片段。同种异体反应性T细胞也表现出对MHC分子的特异性，各种报告表明，MHC分子的残基至少构成了同种异体反应性T细胞受体结合1-4的配体的一部分。人类MHC I类分子的X射线晶体结构，人类MHC-A25，已经提供了证据，加强了MHC结合的自肽6也可能有助于这种识别的论点。我们现在为此提供了直接证据，表明至少一些同种异体反应性细胞毒性T淋巴细胞克隆识别来自细胞质蛋白的多肽片段。我们推测，如果自体多肽参与同种异体识别，则其中一些多肽的序列可能因物种而异，导致相关配体的物种限制性分布(S)8-11。由小鼠细胞系EL4表达的几个针对H-2Kb的同种反应性细胞毒性T淋巴细胞克隆不能裂解表达H-2Kb分子的人细胞转染体(Jurkat-Kb细胞)。然而，这些克隆能够裂解经溴化氰裂解的EL4细胞质提取物预育致敏的Jurkat-Kb细胞。这种提取物的致敏活性被蛋白酶破坏，似乎是由于一种由10到15个氨基酸组成的多肽所致。
ANTIGEN-specific T lymphocytes appear to recognize foreign antigens in the form of peptide fragments presented within the antigen-binding groove of class I or class II molecules encoded by the major histocompatibility complex (MHC). Alloreactive T cells also show specificity for MHC molecules, and various reports suggest that residues of the MHC molecules constitute at least part of the ligand to which alloreactive T-cell receptors bind1–4. The X-ray crystal structure of the human MHC class I molecule, HLA-A25, has provided evidence to strengthen the argument that MHC-bound self-peptide6might also contribute to such recognition7. We now provide direct evidence for this, showing that at least some alloreactive cytotoxic T lymphocyte clones recognize peptide fragments derived from cytoplasmic proteins. We reasoned that if self-peptides were involved in allorecognition, then the sequence of some of these peptides could vary between species, resulting in species-restricted distribution of the relevant ligand (s)8–11. Several alloreactive cytotoxic T lymphocyte clones specific for H–2Kb, expressed by the murine cell line EL4, did not lyse a human-cell transfectant expressing the H–2Kbmolecule (Jurkat-Kbcells). However, these clones were able to lyse Jurkat-Kbcells sensitized by preincubation with an EL4 cytoplasmic extract cleaved by cyanogen bromide. The sensitizing activity from this extract was destroyed by protease and appeared to be due to a peptide consisting of 10 to 15 amino acids.