Loh D Y
Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
New Biol. 1991 Oct;3(10):924-32.
Antigen-specific T lymphocytes recognize peptide antigens in conjunction with the products of the self major histocompatibility complex (MHC). In addition, they are immunologically self-tolerant. To acquire these characteristics, thymocytes undergo a stringent cellular selection process during development. The study of thymocyte development at the molecular level is impeded in mammalian systems by the heterogeneity of the thymocyte population in each individual. However, the use of mice transgenic for the T-cell receptor successfully circumvented this problem and made it possible to elucidate some of the requirements for positive selection, which leads to thymocyte differentiation, survival, and MHC restriction, and negative selection, which leads to programmed cell death, clonal deletion, and self-tolerance. T-cell fate is determined primarily by the nature of the interaction between a complex composed of the T-cell receptor and CD4 or CD8 molecules on the T-cell surface and the peptide antigens that are bound to MHC products and are displayed by other nonlymphoid cells present in the thymus. The molecular analysis of the receptor-ligand interactions involved in this process in transgenic mice provides opportunities to dissect cell fate determination in an intact mammalian system and to understand the molecular basis for immunological self-tolerance and MHC-restriction.
抗原特异性T淋巴细胞识别与自身主要组织相容性复合体（MHC）产物结合的肽抗原。此外，它们具有免疫自身耐受性。为了获得这些特性，胸腺细胞在发育过程中经历严格的细胞选择过程。在哺乳动物系统中，由于每个个体胸腺细胞群体的异质性，在分子水平上对胸腺细胞发育的研究受到阻碍。然而，利用T细胞受体转基因小鼠成功地规避了这个问题，并使得阐明阳性选择（导致胸腺细胞分化、存活和MHC限制）和阴性选择（导致程序性细胞死亡、克隆清除和自身耐受）的一些要求成为可能。T细胞命运主要由T细胞表面由T细胞受体和CD4或CD8分子组成的复合物与结合到MHC产物并由胸腺中存在的其他非淋巴细胞展示的肽抗原之间相互作用的性质决定。对转基因小鼠中参与这一过程的受体-配体相互作用的分子分析，为在完整的哺乳动物系统中剖析细胞命运决定以及理解免疫自身耐受和MHC限制的分子基础提供了机会。
