POSITIVE AND NEGATIVE SELECTION OF LYMPHOCYTES-T
POSITIVE AND NEGATIVE SELECTION OF LYMPHOCYTES-T
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DOI：
10.1101/sqb.1989.054.01.018
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发表时间：
1989-01-01
期刊：
影响因子：
--
通讯作者：
RUSSELL, JH
中科院分区：
文献类型：
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作者：
LOH, DY;SHA, WC;RUSSELL, JH
功能性T淋巴细胞的前体起源于骨髓，并迁移到胸腺，以经历产生功能性T细胞的必要发育事件。一旦在胸腺内，编码抗原特异性T细胞受体（TCR）的基因以高度调节的方式经历体细胞DNA重排。由此产生的细胞表面TCR允许分化中的胸腺细胞与胸腺中展示的多态性主要组织相容性复合体（MHC）的产物相互作用，从而允许”胸腺教育”发生。该过程的最终结果是在外周中存在TCR库，其倾向于在自身MHC分子的背景下识别抗原（MHC限制），以及消除与自身MHC反应”太强”的T细胞（自身耐受性）。此外，CD4或CD8分子的表面表达将外周T细胞分成与限制性MHC分子的性质严格相关的相互排斥的亚群。最后，据估计，只有百分之几的分裂胸腺细胞实际上迁移到外周，他们中的大多数死亡的胸腺选择的结果。为了在细胞和分子水平上研究这些胸腺内发育事件，我们制作了具有已知抗原特异性的TCR分子的转基因小鼠，其命运可以通过使用抗克隆型单克隆抗体（MAb）来跟踪。
Precursors of functional T lymphocytes originate in the bone marrow and migrate to the thymus to undergo the necessary developmental events that result in functional T cells. Once within the thymus, genes encoding the antigen-specific T-cell receptor (TCR) undergo somatic DNA rearrangements in a highly regulated manner. The resulting cell-surface TCR allows the differentiating thymocytes to interact with the products of the polymorphic major histocompatibility complex (MHC) displayed in the thymus, allowing" thymic education" to take place. The end result of this process is the presence in the periphery of a TCR repertoire that is skewed toward recognition of antigens in the context of self-MHC molecules (MHC restriction), as well as elimination of T cells that react" too strongly" with self-MHC (self-tolerance). In addition, surface expression of the CD4 or CD8 molecule divides peripheral T cells into mutually exclusive subsets correlating strictly with the nature of the restricting MHC molecules. Lastly, it has been estimated that only a few percent of the dividing thymocytes actually emigrate into the periphery, the majority of them dying as a result of thymic selection. To study these intrathymic developmental events at the cellular and molecular levels, we have made transgenic mice bearing a TCR molecule of known antigenic specificity whose fate can be followed by using an anticlonotypic monoclonal antibody (MAb).