Moingeon P, Lucich J L, McConkey D J, Letourneur F, Malissen B, Kochan J, Chang H C, Rodewald H R, Reinherz E L
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1492-6. doi: 10.1073/pnas.89.4.1492.
In T lymphocytes, signal transduction through the CD2 adhesion molecule requires surface expression of the CD3-Ti T-cell receptor (TCR) complex. In contrast, in natural killer (NK) cells, CD2 functions in the absence of a TCR. Because the TCR on T lymphocytes and the CD16 low-affinity IgG Fc receptor (Fc gamma receptor type III) complex on NK cells share a common CD3 zeta subunit, we reasoned that CD3 zeta may be critical for CD2 signaling in T lymphocytes and NK cells. Here we show that transfection of a cDNA encoding a transmembrane form of CD16 into TCR- variants of the Jurkat T-cell line results in CD16 expression in association with endogenous CD3 zeta homodimers and restores CD2 signaling function. To test directly the role of CD3 zeta in CD2 triggering, we then transfected human CD2 into each of two murine T-T hybridomas that express TCRs containing either a full-length CD3 zeta subunit or a truncated CD3 zeta subunit incapable of transducing signals. Despite expression of equivalent surface levels of TCR, CD2-mediated signaling is seen only in the T cells containing wild-type CD3 zeta. These findings show that (i) CD16 on NK cells is functionally equivalent to the TCR on T lymphocytes for coupling CD2 to signaling pathways and (ii) CD2 signal transduction depends upon the CD3 zeta subunit of the TCR complex and, by inference, the CD3 zeta subunit of the CD16 complex.
在T淋巴细胞中，通过CD2黏附分子进行信号转导需要CD3-Ti T细胞受体（TCR）复合物的表面表达。相比之下，在自然杀伤（NK）细胞中，CD2在没有TCR的情况下发挥作用。由于T淋巴细胞上的TCR与NK细胞上的CD16低亲和力IgG Fc受体（Fcγ受体III型）复合物共享一个共同的CD3ζ亚基，我们推测CD3ζ可能对T淋巴细胞和NK细胞中的CD2信号传导至关重要。在这里我们表明，将编码跨膜形式CD16的cDNA转染到Jurkat T细胞系的TCR变体中，会导致CD16与内源性CD3ζ同二聚体结合表达，并恢复CD2信号传导功能。为了直接测试CD3ζ在CD2触发中的作用，我们随后将人CD2转染到两种小鼠T-T杂交瘤中的每一种中，这两种杂交瘤表达的TCR分别含有全长CD3ζ亚基或无法转导信号的截短CD3ζ亚基。尽管TCR的表面表达水平相当，但CD2介导的信号传导仅在含有野生型CD3ζ的T细胞中可见。这些发现表明：（i）NK细胞上CD16在将CD2与信号传导途径偶联方面在功能上等同于T淋巴细胞上的TCR；（ii）CD2信号转导取决于TCR复合物的CD3ζ亚基，据此推断，也取决于CD16复合物的CD3ζ亚基。
