MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们对人类T细胞识别的研究强调两个基本领域：1） 识别和表征细胞表面分子的功能 促进T细胞识别;和2）分析 人T细胞的亚群和这些亚群的功能能力。 主要的新发现涉及T细胞与细胞外基质的相互作用 (ECM)件.静息T细胞在其表面上表达三个成员， VLA（β 1）整联蛋白家族，并可通过三种不同途径粘附于ECM VLA介导的途径：VLA-4/纤连蛋白、VLA-5/纤连蛋白、VLA-6/层粘连蛋白。 通过这些途径的结合受两种不同且互补的 其作用机制：1）VLA受体的表达受T细胞介导的调节， 2）受体的功能能力迅速增强， 监管.因为我们发现这些受体也促进了 体外T细胞，它们不仅对T细胞， 粘附/迁移，但也在T细胞活化。的机制 粘附力的调节正在研究中;一种可能性是 探索的是快速活化诱导的细胞表面脱落 分子调节T细胞粘附。同时进行的研究扩大了我们的 了解涉及其他附件的通路的重要性 分子促进T细胞活化。T细胞的系统分析 LFA-1与生物化学纯化的配体ICAM-1的相互作用强调了LFA-1与ICAM-1的相互作用。 这种分子相互作用作为T细胞共刺激物的有效作用 activation.此外，分析单核细胞的共刺激作用， T细胞受体介导的活化表现出重要的贡献， 不仅LFA-I/ICAM-1，而且CD 2/LFA-3和目前研究的其他分子也是如此。 调查新的T细胞亚群已经用mAb特异性 CD 45 RB抗原该标记物允许区分两个亚组的 记忆T细胞，其功能能力正在研究中。 系统定量分析多种分子在 来自正常人和艾滋病患者的T细胞表面继续揭示新的 T细胞亚群的异质性，其生理相关性现在正在被 研究了

Our studies of human T cell recognition emphasize two fundamental areas: 1) identifying and characterizing the functions of cell surface molecules which facilitate T cell recognition; and 2) analysis of heterogeneity among subsets of human T cells and of the functional capacities of those subsets. Major new findings relate to T cell interaction with extracellular matrix (ECM) components. Resting T cells express on their surface three members of the VLA (beta1) integrin family and can adhere to ECM via three distinct VLA-mediated pathways: VLA-4/fibronectin, VLA-5/fibronectin, VLA-6/laminin. Binding via these pathways is regulated by two distinct and complementary mechanisms: 1) Expression of the VLA receptors is regulated with T cell differentiation; 2) the functional capacity of the receptors is rapidly regulated. Since we find that these receptors also facilitate activation of the T cells in vitro, they may be important not only in T cell adhesion/migration, but also in T cell activation. The mechanisms for regulation of adhesion are under investigation; one possibility being explored is that rapid activation-induced shedding of cell surface molecules modulates T cell adhesion. Concurrent studies have extended our understanding of the importance of pathways involving other accessory molecules in facilitating T cell activation. Systematic analyses of T cell LFA-1 interaction with biochemically purified ligand ICAM-1 emphasize the potent role of this molecular interaction as a costimulus for T cell activation. Furthermore, analysis of the costimulatory role of monocytes in T-cell receptor-mediated activation demonstrate important contributions not only of LFA-I/ICAM-1 but also CD2/LFA-3 and other molecules currently under investigation. New subsets of T cells have been defined with a mAb specific for the CD45RB antigen. This marker allows discrimination of two subsets of memory T cells, whose functional capacities are under investigation. Systematic quantitative analysis of expression of many molecules on the surface of T cells from normals and AIDS patients continue to reveal new heterogeneity of T cell subsets, whose physiological relevance is now being investigated.