The functional role of class II-associated invariant chain peptide (CLIP) in its ability to variably modulate immune responses
The functional role of class II-associated invariant chain peptide (CLIP) in its ability to variably modulate immune responses
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DOI：
10.1093/intimm/12.6.757
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发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Singh, B
中科院分区：
文献类型：
--
作者：
Chaturvedi, P;Hengeveld, R;Singh, B
固化II类MHC组装和细胞表面表达的过程，将II类相关的不变链肽（CLIP）从MHC的肽结合沟中去除，这是由H-2M介导的任务，这允许肽表位的结合和呈递，我们之前已经表明，外源添加的CLIP会干扰这一过程并下调II类分子的细胞表面表达。在本研究中，我们探讨了外源添加的 CLIP 对抗原特异性免疫反应的影响。使用 CLIP 以及对 I-A(d) 分子具有不同亲和力的各种肽和蛋白质抗原进行的体内研究表明，CLIP 对 T 细胞介导的免疫反应有不同的影响。根据细胞因子谱和抗体同种型确定，用 CLIP 与抗原一起进行免疫诱导从 T(h)1 样反应转变为 T(h)2 样反应。这些结果表明，外源 CLIP 的存在可以显着影响 II 类 MHC 分子向 CD4 T 细胞呈递抗原，从而调节免疫反应。外源添加的 CLIP 迅速定位到存在 MHC II 类分子的抗原呈递细胞的亚细胞区室中。我们认为外源 CLIP 减少了 II 类分子上肽的负载，从而下调细胞表面的 MHC-肽复合物。或者，CLIP 可以与细胞表面 II 类分子结合，并且该复合物快速内化，导致细胞表面 MHC II 类表达减少。 MHC-肽复合物水平的降低有利于 T(h)2 细胞比 T(h)1 细胞激活。这些结果对免疫反应的调节具有重要意义，特别是预防某些自身免疫性疾病，其中 T(h)1 型反应是致病性的，T(h)2 型反应是保护性的。
Curing the process of class II MHC assembly and cell surface expression, the class Ii-associated invariant chain peptide (CLIP) is removed from the peptide-binding groove of MHC, a task mediated by H-2M, This allows binding and presentation of peptide epitopes, We have previously shown that exogenously added CLIP interferes with this process and down-regulates the cell surface expression of class II molecules. In this study, we explored the effect of exogenously added CLIP on antigen-specific immune responses. In vivo studies with CLIP and various peptide and protein antigens with different affinities for I-A(d) molecules demonstrated that CLIP variably affects the T cell-mediated immune responses. Immunization with CLIP along with the antigen induced a shift from a T(h)1- to T(h)2-like response as determined by the cytokine profile and antibody isotype, These results suggest that the presence of exogenous CLIP can significantly influence the presentation of antigen by class II MHC molecules to CD4 T cells and thereby modulate immune responses. Exogenously added CLIP rapidly localized into the subcellular compartment of antigen-presenting cells where MHC class II molecules are present. We suggest that exogenous CLIP reduces the loading of peptides on the class II molecules, thus down-regulating MHC-peptide complexes on the cell surface. Alternatively, CLIP may bind to cell surface class II molecules and this complex is rapidly internalized resulting in reduced cell surface MHC class II expression. The reduced level of MHC-peptide complexes favors the activation of T(h)2 cells over T(h)1 cells. These results have implications in the regulation of immune responses, particularly the prevention of certain autoimmune diseases where T(h)1-type responses are pathogenic and T(h)2-type responses are protective.