Mentzer S J, Smith B R, Barbosa J A, Crimmins M A, Herrmann S H, Burakoff S J
J Immunol. 1987 Mar 1;138(5):1325-30.
Th initial step in cytolytic T lymphocyte (CTL)-mediated cytolysis involves target cell adhesion and antigen recognition. To investigate these initial events in the CTL-target interaction, we used HLA-A2- and HLA-B7-specific human CTL clones and HLA-typed B lymphoblastoid target cells. By using two different adhesion assays, we demonstrated antigen nonspecific CTL-target cell adhesion. To more precisely define the contribution of the antigen-specific receptor to CTL-target cell adhesion, we used the HLA-A2, HLA-B7, and mock transfected RD target cells. Consistent with the results when using B lymphoblastoid target cells, the CTL clones demonstrated equivalent adhesions to the RD target cells whether or not they expressed HLA-A2 or HLA-B7. These results suggested that CTL-target cell adhesion occurred independent of the T cell receptor. By using the calcium-sensitive dye Indo-1 and flow cytometry, we assessed CTL-target cell adhesion and CTL activation. Simultaneous measurement of adhesion and intracellular free calcium demonstrated that CTL-target cell adhesion alone did not activate CTL clones. Both CTL-target cell adhesion and the presence of the appropriate HLA target molecule were necessary for the efficient activation of human CTL. MAb inhibition studies indicated that antigen nonspecific adhesion is largely regulated by the LFA-1, CD2 (LFA-2/T11), and LFA-3 cell surface molecules. These antigen nonspecific cell-cell interaction molecules appear to play an important role in facilitating antigen recognition and subsequent target cell lysis.
细胞毒性T淋巴细胞(CTL)介导的细胞溶解的初始步骤涉及靶细胞黏附和抗原识别。为了研究CTL与靶细胞相互作用中的这些初始事件,我们使用了HLA - A2和HLA - B7特异性的人CTL克隆以及HLA分型的B淋巴母细胞靶细胞。通过使用两种不同的黏附测定方法,我们证明了抗原非特异性的CTL - 靶细胞黏附。为了更精确地确定抗原特异性受体对CTL - 靶细胞黏附的贡献,我们使用了HLA - A2、HLA - B7和mock转染的RD靶细胞。与使用B淋巴母细胞靶细胞时的结果一致,CTL克隆对RD靶细胞的黏附情况相同,无论RD靶细胞是否表达HLA - A2或HLA - B7。这些结果表明,CTL - 靶细胞黏附的发生独立于T细胞受体。通过使用钙敏感染料Indo - 1和流式细胞术,我们评估了CTL - 靶细胞黏附和CTL激活情况。同时测量黏附和细胞内游离钙表明,仅CTL - 靶细胞黏附不会激活CTL克隆。CTL - 靶细胞黏附和适当的HLA靶分子的存在对于人CTL的有效激活都是必需的。单克隆抗体抑制研究表明,抗原非特异性黏附在很大程度上受LFA - 1、CD2(LFA - 2/T11)和LFA - 3细胞表面分子的调节。这些抗原非特异性细胞间相互作用分子似乎在促进抗原识别和随后的靶细胞裂解中起重要作用。