第二章抗原.ppt.ppt

通常，普通蛋白质抗原可激活机体总T细胞库中万分之一至百万分之一的T细胞。然而，某些抗原物质，只需要极低浓度（1~10ng/ml）即可激活2％~20％T细胞克隆，产生极强的免疫应答，这类抗原称之为超抗原（superantigen,SAg），其主要特性如表3-5所示。与普通蛋白质抗原不同，SAg的一端可直接与TCR的Vβ链CDR3外侧区域结合，以完整蛋白的形式激活T细胞，另一端则与抗原提呈细胞表面的MHCⅡ类分子的抗原结合槽（cleft）外部结合，因而SAg不涉及Vβ的CDR3及TCRα的识别，也不受MHC的限制。SAg所诱导的T细胞应答，其效应并非针对超抗原本身，而是通过分泌大量的炎症性细胞因子而参与某些严重病理生理过程(导致中毒性休克、多器官衰竭、自身组织损伤)的发生与发展。因此，超抗原实际为一类多克隆激活剂。 SAg主要有外源性超抗原和内源性超抗原两类。前者如金黄色葡萄球菌肠毒素A~E(staphylococcus enterotoxin A~E, SEA~SEE)；后者如小鼠乳腺肿瘤病毒蛋白，它表达在细胞表面，作为次要淋巴细胞刺激抗原（minor lymphocyte stimulating antigen, mls）,刺激T细胞增殖（图3-3）。近年亦发现有作用于TCRγδ+T细胞的超抗原如热休克蛋白（heat shock protein，HSP），以及和B细胞超抗原如金黄色葡萄球菌蛋白A(staphylococcus protein A，SPA)和人类免疫缺陷病毒（human immumodeficency virus，HIV）gp120。它们活化γδ+T细胞和B细胞的机制目前尚不完全清楚。 Figure 16-2:?Polyclonal activation of T cells by bacterial superantigens. A,?Conventional microbial T cell antigens, composed of a peptide bound to the peptide-binding groove of an MHC molecule, are recognized by a very small fraction of T cells in any one individual, and only these T cells are activated to become effector T cells that protect against the microbe.?B,?In contrast, a superantigen binds to class II MHC molecules outside the peptide-binding groove and simultaneously binds to the variable region of different TCR β chains, regardless of the peptide specificity of the TCR. Different superantigens bind to TCRs of different Vβ families. Because many T cells express a TCR β chain from a particular Vβ family, superantigens can activate a large number of T cells. In the example shown, the superantigen staphylococcal enterotoxin B (SEB) binds to HLA-DR and the V regions of TCRs belonging to the Vβ3 family.? Certain bacterial toxins stimulate all T cells in an individual that express a particular family of Vβ?T cell receptor (TCR) genes. Such toxins are called superantigens?because they resemble antigens in that they bind to TCRs and to class II MHC molecules (although not to the peptide-binding clefts) but activate many more T cells than do conventional peptide