MHC-independent T cells

MHC非依赖性T细胞

• 批准号: 8349338
• 负责人: Alfred Singer
• 金额: $ 78.18万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349338
• 关键词: Antibodies; Antigens; Binding; CD8B1 gene; Cells; Detection; Goals; Ligands; Major Histocompatibility Complex; Malignant Neoplasms; Mus; Protein Tyrosine Kinase; Role; Signal Transduction; Specificity; T-Lymphocyte; Testing; Thymus Gland; Transgenes; base; in vivo; molecular shape; prevent; thymocyte

The thymus produces MHC-restricted abT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that CD4 and CD8 coreceptors might be impose MHC-specificity on a broader abTCR repertoire during thymic selection because they bind and effectively sequester the tyrosine kinase Lck, thereby preventing TCR signaling by non-MHC ligands that do not engage either coreceptor. Using mice deficient for both CD4 and CD8 as well as MHC (Quad-deficient), we discoverd that ab thymocytes can be signaled by non-MHC ligands in the absence of coreceptors in vivo. In addition, we tested the critical role of coreceptors by introducing CD4 transgenes into Quad-deficient mice. Whereas sequestration of Lck by wild-type CD4 blocked signaling by non-MHC ligands on ab thymocytes, introducing a tailless form of CD4 didnt. We conclude that in the absence of Lck sequestration by coreceptors, thymocytes can be signaled by non-MHC ligands. Therefore, CD4 and CD8 impose MHC-specificity on a broad abTCR repertoire by preventing thymocytes to be selected by non-MHC ligands.

胸腺产生的MHC限制性ABT细胞仅识别与MHC或MHC样分子相关的抗原配体。我们假设CD4和CD8共受体可能在胸腺选择过程中施加MHC特异性，因为它们结合并有效地隔离了酪氨酸激酶LCK并有效地隔离了酪氨酸激酶LCK，从而防止了不吸引corecector的非MHC配体TCR信号传导。使用缺乏CD4和CD8的小鼠以及MHC（四肢），我们发现在体内没有共肽的情况下，非MHC配体可以通过非MHC配体发出AB胸腺细胞。此外，我们通过将CD4转基因引入四肢缺陷的小鼠中测试了共感染者的关键作用。而野生型CD4将LCK固定在AB胸腺细胞上的非MHC配体阻断信号传导，引入了CD4的尾灯形式。我们得出的结论是，在没有共感染者的LCK隔离的情况下，胸腺细胞可以通过非MHC配体发出信号。因此，CD4和CD8通过防止非MHC配体选择胸腺细胞，将MHC特异性施加在广泛的ABTCR曲目上。