Abe R, Foo-Phillips M, Granger L G, Kanagawa O
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1992 Dec 1;149(11):3429-39.
In addition to Mlsa (Mls-1a) and Mlsc (Mls-2a, Mls-3a), we and others have recently described a third set of stimulatory minor lymphocyte stimulating (Mls) determinants, which are ligands for "I-E related" V beta, V beta 5, V beta 11, and V beta 12. Although all V beta associated with the recognition of the conventional Mls determinants are, in general, uniformly deleted in those animals expressing relevant Mls, expression of Mlsf-related V beta reveals various deletion patterns among different strains. Here we describe extensive genetic studies to evaluate the relationship among the self-Ag responsible for clonal deletion of T cells bearing Mlsf-related V beta by using antibodies specific for TCR V beta chain. In addition, a panel of T cell clones specific for the Mlsf determinant were generated and employed to analyze the determinant specificity, which is recognized by Mlsf-reactive T cells in vitro as well as the role of class II molecules in T cell recognition of the Mlsf determinants. The results of these two independent approaches provide evidence that the Mlsf system is composed of a set of gene products that reveal a unique polymorphism in the induction of clonal deletion in vivo and in T cell activation in vitro. One of these gene products causes almost complete deletion of the self-Mlsf reactive T cell repertoire in vivo and elicits a strong proliferative response to Mlsf-specific T cell clones. Expression of the other gene products results in the clonal deletion of only part of the Mlsf-reactive T cell repertoire. Furthermore, the response pattern of Mlsf-specific clones to intra-MHC recombinant inbred strains and the inhibition pattern of these clones by anti-class II antibody suggested that although expression of the I-E molecule is essential for T cell recognition of Mlsf determinants, the A beta gene may also contribute to the efficient presentation of Mlsf determinants by forming unique class II E alpha A beta molecules.
除了Mlsa（Mls-1a）和Mlsc（Mls-2a、Mls-3a）之外，我们和其他研究人员最近描述了第三组刺激性小淋巴细胞刺激（Mls）决定簇，它们是“I-E相关”Vβ、Vβ5、Vβ11和Vβ12的配体。尽管与传统Mls决定簇识别相关的所有Vβ在表达相关Mls的动物中通常会被一致删除，但与Mlsf相关的Vβ的表达在不同品系中显示出各种删除模式。在此，我们描述了广泛的遗传学研究，以利用针对TCR Vβ链的特异性抗体评估负责带有Mlsf相关Vβ的T细胞克隆性删除的自身抗原之间的关系。此外，还产生了一组针对Mlsf决定簇的T细胞克隆，并用于分析决定簇特异性，该决定簇在体外被Mlsf反应性T细胞识别，以及II类分子在T细胞识别Mlsf决定簇中的作用。这两种独立方法的结果提供了证据，表明Mlsf系统由一组基因产物组成，这些基因产物在体内克隆性删除的诱导和体外T细胞活化中显示出独特的多态性。其中一种基因产物在体内几乎导致自身Mlsf反应性T细胞库的完全删除，并引发对Mlsf特异性T细胞克隆的强烈增殖反应。其他基因产物的表达仅导致部分Mlsf反应性T细胞库的克隆性删除。此外，Mlsf特异性克隆对MHC内重组近交系的反应模式以及这些克隆被抗II类抗体的抑制模式表明，尽管I-E分子的表达对于T细胞识别Mlsf决定簇至关重要，但Aβ基因也可能通过形成独特的II类EαAβ分子，有助于Mlsf决定簇的有效呈递。
