MECHANISMS OF HUMAN IN VITRO CELLULAR IMMUNE RESPONSES

我们已经研究了CTL-靶相互作用，使用了具有良好特征的克隆 人类CTL。这些CTL与多种抗原阴性的偶联反应 目标几乎与使用特定的目标单元一样有效，但不是 导致靶细胞裂解。这些发现表明，在特定的目标上 细胞，通过抗原非依赖途径的黏附可能同时发生 或先于抗原识别。我们的MAB抑制研究使用 单个单抗和混合：1)证明CD18、CD2和LFA-3是 参与抗原非依赖性结合物的形成；以及2)提示 CD2和LFA-3分子参与一条途径，而CD18 分子参与了一条不同的途径。对存在的确认 CD18依赖的黏附的发现提供了不同的途径 需要阳离子，对温度敏感，而CD2-和 依赖LFA-3的黏附不需要阳离子和IS 对温度不敏感。结合之前的数据，这些研究 强烈提示效应器上的CD2可能与LFA-3相互作用 配基对准目标。LFA-3蛋白的纯化正在进行中。 LFA-3基因的克隆正试图通过“鸟枪式”转基因和 通过寡核苷酸探查一个cDNA.

We have explored CTL-target interactions using well characterized cloned human CTL. Conjugate formation between these CTL and many antigen-negative targets is almost as efficient as with specific target cells, but does not lead to target cell lysis. These findings suggest that, on specific target cells, adhesion by antigen-independent pathways may occur concurrently with or precede antigen recognition. Our MAB inhibition studies using individual MAB and mixes: 1) demonstrate that CD18, CD2, and LFA-3 are involved in antigen-independent conjugate formation; and 2) suggest that the CD2 and LFA-3 molecules are involved in one pathway and the CD18 molecule is involved in a distinct pathway. Confirmation of the existence of distinct pathways was provided by findings that CD18-dependent adhesion requires cations and is temperature-sensitive while CD2- and LFA-3-dependent adhesion does not require cations and is temperature-insensitive. Together with previous data, these studies strongly suggest that CD2 on the effector may interact with LFA-3 as its ligand on targets. Purification of the LFA-3 protein is in progress. Cloning of the LFA-3 gene is being attempted by "shotgun" transfection and by oligonucleotide probing of a cDNA.