Rust C J, Koning F, van Schooten W C
ImmuLogic Phar. Corp., Palo Alto, California 94304.
Cell Immunol. 1993 Oct 15;151(2):467-73. doi: 10.1006/cimm.1993.1255.
We investigated the role of HLA-DR molecules in T cell stimulation by staphylococcal enterotoxin A (SEA). Previous results with immobilized purified HLA-DR preincubated with peptide showed that peptide-specific T cell clones were able to bind to and proliferate in response to purified HLA-DR/peptide complexes in the absence of antigen presenting cells. We report here that two human T cell clones (1 alpha beta and 1 gamma delta T cell clone) and a murine T cell hybridoma were each activated by immobilized purified HLA-DR4Dw4 preincubated with SEA. Furthermore, immobilized SEA in the absence of HLA-DR4Dw4 also stimulated the human T cell clones. The proliferative response of the human T cell clones was inhibited by CD3-reactive monoclonal antibodies, indicating that the T cell receptor (TCR)/CD3 reacts with SEA. These observations suggest that the HLA-DR in the complex functions only to immobilize SEA and that an interaction between the TCR and HLA-DR is not necessary for SEA-driven T cell stimulation. Finally, the assays described here could provide a method for defining and distinguishing the SEA binding sites for MHC class II and TCR.
我们研究了HLA - DR分子在葡萄球菌肠毒素A(SEA)刺激T细胞过程中的作用。先前的研究结果表明,将固定化的纯化HLA - DR与肽预孵育后,肽特异性T细胞克隆能够在无抗原呈递细胞的情况下,与纯化的HLA - DR/肽复合物结合并增殖。我们在此报告,两种人类T细胞克隆(1个αβ T细胞克隆和1个γδ T细胞克隆)以及1个小鼠T细胞杂交瘤,分别被与SEA预孵育的固定化纯化HLA - DR4Dw4激活。此外,在无HLA - DR4Dw4的情况下,固定化的SEA也能刺激人类T细胞克隆。人类T细胞克隆的增殖反应受到CD3反应性单克隆抗体的抑制,这表明T细胞受体(TCR)/CD3与SEA发生了反应。这些观察结果表明,复合物中的HLA - DR仅起到固定SEA的作用,并且SEA驱动的T细胞刺激并不需要TCR与HLA - DR之间的相互作用。最后,本文所述的检测方法可为定义和区分MHC II类分子与TCR的SEA结合位点提供一种方法。