Rudd C E, Barber E K, Burgess K E, Hahn J Y, Odysseos A D, Sy M S, Schlossman S F
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Adv Exp Med Biol. 1991;292:85-96. doi: 10.1007/978-1-4684-5943-2_10.
The CD4 and CD8 antigens on the surface of T cells appear to bind to major histocompatibility complex (MHC) class II and I antigens, respectively. These antigens also synergize with the Ti(TcR)/CD3 complex in the potentiation of T-cell proliferation. Our earlier work demonstrated that the CD4 and CD8 receptors are coupled to a protein-tyrosine kinase termed p56lck from normal and transformed T lymphocytes. The p56lck protein is a member of the src family and its homology with receptor-kinases such as the epidermal growth factor receptor (EGFR) make it an important candidate in signal transduction. In this paper, we show in transfectants that p56lck interacts with the cytoplasmic tail of the CD4 antigen. Murine p56lck can interact across species with the human CD4 receptor. Furthermore, peptide competition studies showed that a specific sequence within the cytoplasmic tail of CD4 interacts with the kinase. Cysteine residues also appear to play key roles in this interaction. Lastly, we show biochemically that the CD4:p56lck complex can physically associate with the epsilon chain of the CD3 complex on HPB-ALL transformed T cells. This interaction may provide a bridge by which events related to ligand binding to Ti(TcR)/CD3 may trigger T cells via the CD4/CD8:p56lck complex.
T细胞表面的CD4和CD8抗原似乎分别与主要组织相容性复合体（MHC）II类和I类抗原结合。这些抗原还与Ti（TcR）/CD3复合体协同作用，增强T细胞增殖。我们早期的研究表明，CD4和CD8受体与正常和转化的T淋巴细胞中一种名为p56lck的蛋白酪氨酸激酶偶联。p56lck蛋白是src家族的成员，其与表皮生长因子受体（EGFR）等受体激酶的同源性使其成为信号转导中的重要候选者。在本文中，我们在转染细胞中表明p56lck与CD4抗原的胞质尾部相互作用。小鼠p56lck可跨物种与人CD4受体相互作用。此外，肽竞争研究表明，CD4胞质尾部的特定序列与该激酶相互作用。半胱氨酸残基似乎在这种相互作用中也起着关键作用。最后，我们通过生化方法表明，CD4:p56lck复合体可与HPB-ALL转化T细胞上CD3复合体的ε链物理缔合。这种相互作用可能提供了一座桥梁，通过它与配体结合到Ti（TcR）/CD3相关的事件可能经由CD4/CD8:p56lck复合体触发T细胞。
