Takai Y, Reed M L, Burakoff S J, Herrmann S H
Department of Pathology, Dana-Farber Cancer Institute, Boston, MA.
Proc Natl Acad Sci U S A. 1987 Oct;84(19):6864-8. doi: 10.1073/pnas.84.19.6864.
The recognition of foreign antigen by T lymphocytes requires direct contact with cells expressing the antigen. It has recently become clear that T lymphocytes can form conjugates with other cells in the absence of foreign antigen expression. Studies using monoclonal antibodies (mAbs) to inhibit conjugate formation have suggested that a portion of the antigen-dependent adhesion is mediated by T lymphocytes interacting with cells expressing lymphocyte-function-associated antigen 3 (LFA-3), a widely distributed cell surface protein. We have investigated antigen-independent adhesion by incorporating affinity-purified LFA-3 into the lipid membrane of an artificial target cell (ATC; a nylon-matrix vesicle with a lipid membrane). These vesicles are similar in size and density to intact cells, so that conjugates between cells and ATCs may be seen by light microscopy. ATCs expressing a density of LFA-3 similar to that on intact cells were found to form conjugates with T cells, but only if the T cells expressed the sheep erythrocyte receptor, CD2 (T11; LFA-2). Previous studies using mAbs have implicated the CD2 molecule in both adhesion and T-cell activation. ATCs prepared without surface protein or with purified HLA class I protein failed to interact with the CD2-positive T cells, indicating that the adhesion found was mediated by the LFA-3 molecule. Furthermore, mAb against LFA-3 or CD2 was able to block the LFA-3-mediated vesicle-cell interaction, whereas mAb against LFA-1 or HLA failed to inhibit the interaction. These results provide direct evidence that LFA-3 functions as an adhesion molecule by serving as a ligand for the CD2 molecule on T cells.
T淋巴细胞识别外来抗原需要与表达该抗原的细胞直接接触。最近已经明确，在没有外来抗原表达的情况下，T淋巴细胞也能与其他细胞形成共轭体。使用单克隆抗体（mAb）抑制共轭体形成的研究表明，部分抗原依赖性黏附是由T淋巴细胞与表达淋巴细胞功能相关抗原3（LFA-3，一种广泛分布的细胞表面蛋白）的细胞相互作用介导的。我们通过将亲和纯化的LFA-3掺入人工靶细胞（ATC；一种具有脂质膜的尼龙基质囊泡）的脂质膜中来研究抗原非依赖性黏附。这些囊泡在大小和密度上与完整细胞相似，因此细胞与ATC之间的共轭体可以通过光学显微镜观察到。发现表达与完整细胞上密度相似的LFA-3的ATC能够与T细胞形成共轭体，但前提是T细胞表达绵羊红细胞受体CD2（T11；LFA-2）。先前使用mAb的研究表明CD2分子与黏附和T细胞活化都有关。没有表面蛋白或带有纯化的HLA I类蛋白的ATC无法与CD2阳性T细胞相互作用，这表明所发现的黏附是由LFA-3分子介导的。此外，抗LFA-3或CD2的mAb能够阻断LFA-3介导的囊泡-细胞相互作用，而抗LFA-1或HLA的mAb则不能抑制这种相互作用。这些结果提供了直接证据，表明LFA-3作为T细胞上CD2分子的配体发挥黏附分子的作用。
