MECHANISMS OF CELLULAR IMMUNE RESPONSES

我们的研究继续致力于阐明 T细胞识别，特别强调抗原 独立的T细胞粘附作为该过程的关键早期步骤 的认可。 主要进展是在了解 ICAM-1分子的功能作用，我们以前的功能， 功能研究表明其具有作为LFA-1配体的功能。 通过免疫亲和层析纯化ICAM-1。 每个 由单克隆抗体确定的ICAM-1上的两个位点是 与其粘附功能有关。 此外，ICAM-I必须是 粘附配体本身，因为ICAM-1固定在塑料上 介导T、B和骨髓细胞的LFA 1依赖性粘附。 这 细胞与ICAM-1结合的简化系统允许 在重要特征的明确定义的系统中进行隔离/分析 更复杂的细胞相互作用， 阳离子的要求，和解离阶段，发生以下 绑定阶段。 最近的研究证实并扩展了我们以前的研究。 理解人类幼稚细胞和记忆细胞是不同的， 表型上的差异表达不仅是粘附 分子CD 2、LFA-3和LFA-1，而且还包括几种其它分子。 重要的功能分子。 我们已经证明了记忆 T细胞增殖比幼稚细胞多得多时，刺激与 CD 3 mAb或成对的CD 2 mAb。 这种增强的应对能力， 受体介导的触发是T细胞的一种新机制， 可以促进记忆细胞对特定抗原的反应。 此外，通过CD 2或CD 3的刺激导致 通过记忆试验产生大量γ干扰素 细胞，但几乎没有幼稚细胞;因此，从 幼稚记忆细胞似乎伴随着一个稳定的变化， 在γ干扰素基因的调控中。 我们正在鉴定七种新的单克隆抗体， 与前述表型相关的抗体， 功能研究，并似乎确定至少两个新的 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.