Abstract：
CD2 is largely described to promote T cell activation when engaged by its ligands, CD48 in mice and CD58 in humans, that are present on antigen-presenting cells (APCs). However, both CD48 and CD58 are also expressed on T cells. By generating new knockout mouse strains lacking CD2 or CD48 in the C57BL/6 background, we determined that whereas CD2 was necessary on T cells for T cell activation, its ligand CD48 was not required on APCs. Rather, CD48 was also needed on T cells. One exception was during cytotoxicity, which required CD48 on T cells and APCs. Fluorescence resonance energy transfer (FRET) studies in nonimmune cells provided evidence that cis interactions between CD2 and CD48 existed within individual cells. CD2-CD48 interactions on T cells enabled more robust T cell receptor (TCR) signals, including protein tyrosine phosphorylation. Using T cells from a CD2 knock-in mouse in which a tag was inserted at the carboxyl terminus of CD2, mass spectrometry analyses revealed that the role of CD2 in T cell activation correlated with its ability to interact with components of the TCR complex and the protein tyrosine kinase Lck. CD2-CD58 provided a similar function in human T cells. Thus, our data imply that T cell-intrinsic cis interactions of CD2 with its ligands are required for TCR signaling and T cell activation. Interactions with ligands on APCs contribute during cytotoxicity.
摘要：
CD2在很大程度上被描述为通过其配体参与时促进T细胞活化，小鼠中的CD48和人类中的CD58，存在于抗原呈递细胞（APC）上。然而,CD48和CD58也在T细胞上表达。通过在C57BL/6背景中产生缺乏CD2或CD48的新敲除小鼠品系，我们确定CD2是T细胞活化所必需的，APC上不需要其配体CD48。相反，T细胞上也需要CD48。一个例外是在细胞毒性过程中，这需要T细胞和APC上的CD48。非免疫细胞中的荧光共振能量转移（FRET）研究提供了CD2和CD48之间的顺式相互作用存在于单个细胞内的证据。T细胞上的CD2-CD48相互作用使T细胞受体（TCR）信号更强大，包括蛋白酪氨酸磷酸化。使用来自CD2敲入小鼠的T细胞，其中在CD2的羧基末端插入了标签，质谱分析显示，CD2在T细胞活化中的作用与其与TCR复合物和蛋白质相互作用的能力相关。酪氨酸激酶Lck。CD2-CD58在人T细胞中提供相似的功能。因此，我们的数据暗示T细胞固有的CD2与其配体的顺式相互作用是TCR信号传导和T细胞活化所必需的.与APC上的配体的相互作用在细胞毒性期间起作用。
