MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们的研究继续致力于阐明这些机制。 T细胞识别，特别强调抗原 独立的T细胞黏附是这一过程的关键早期步骤 有认同感。主要进展是在理解 细胞间黏附分子-L分子的功能作用 国内的研究表明，LFA-L具有配体的功能。 细胞间黏附分子-L经免疫亲和层析纯化。每个人 由单抗定义的细胞间黏附分子-L上的两个位点是 与其黏附功能有关。此外，ICAM-L必须是 细胞间黏附分子-L固定在塑料上后的黏附配体本身 介导LFA1依赖的T、B细胞和髓系细胞的黏附。这 细胞与细胞间黏附分子结合的简化系统-L允许 在明确定义的重要特征系统中进行隔离/分析 更复杂的细胞相互作用，包括特征二价 阳离子要求，以及随后发生的解离阶段 绑定阶段。最近的研究证实并扩展了我们之前的 理解人类的幼稚和记忆细胞是不同的 表型不仅表现在粘附性表达上的差异 分子CD2、LfA-3和LfA-L，还有其他几种 功能重要的分子。我们已经证明了这一记忆 当T细胞被刺激时，其增殖能力比原始细胞高得多 CD3单抗或CD2单抗对。这种增强的响应能力 受体介导的触发是T细胞的一种新机制，它 可以促进记忆细胞对特定抗原的反应。 此外，通过CD2或CD3刺激会导致 Memory T产生大量的伽马干扰素 细胞，但几乎没有幼稚的细胞；因此与 幼稚的记忆细胞似乎伴随着稳定的变化 对伽马干扰素基因的调控。 我们正在鉴定七个新的单抗 与上述表型相关的抗体和 功能研究，似乎发现了至少两个新的 分子。

Our studies continue to be directed at elucidating the mechanisms of T cell recognition, with particular emphasis on antigen independent T cell adhesion as a critical early step in the process of recognition. Major progress has been in understanding the functional role of the ICAM-l molecule which our previous func- tional studies have suggested functions as a ligand for LFA-l. ICAM-l has been purified by immunoaffinity chromatography. Each of two sites on ICAM-l defined by monoclonal antibodies are implicated in its adhesion function. Furthermore, ICAM-l must be an adhesion ligand per se since ICAM-l immobilized on plastic mediates LFA1 dependent adhesion of T, B and myeloid cells. This simplified system of cell binding to ICAM-l allows isolation/analysis in a well defined system of important features of more complex cell interactions including characteristic divalent cation requirements, and a dissociation phase that occurs following the binding phase. Recent studies confirm and extend our previous understanding that human naive and memory cells are distinguished phenotypically by differences in expression not only of adhesion molecules CD2, LFA-3 and LFA-l, but also of several other functional important molecules. We have demonstrated that memory T cells proliferate much more than naive cells when stimulated with CD3 mAb or pairs of CD2 mAb. Such enhanced responsiveness to receptor-mediated triggering is a novel mechanism for T cells which could facilitate memory cell response to specific antigen. Furthermore, stimulation via either CD2 or CD3 results in substantial amounts of gamma interferon production by memory T cells but virtually none by naive cells; thus differentiation from naive to memory cells appears to be accompanied by a stable change in regulation of the gene for gamma interferon. We are in the process of characterizing seven new monoclonal antibodies which are relevant to the foregoing phenotypic and functional studies and appear to identify at least two new molecules.