St-Pierre Y, Watts T H
Department of Immunology, University of Toronto, Ontario.
J Immunol. 1990 Aug 1;145(3):812-8.
The presentation of protein Ag with MHC class II proteins involves the uptake of the protein Ag by endocytosis followed by processing, probably proteolysis, in an intracellular acidic compartment. However, there remains considerable controversy as to the precise route taken by the antigen and the MHC class II protein during this process. The unusual stability of Ag-MHC class II protein complexes has led to speculation that antigen can only associate with newly synthesized MHC class II molecules. An alternate possibility is that the MHC class II binding site can be regenerated within the cell during internalization and recycling of MHC class II proteins. To address these possibilities, three different murine B lymphoma lines were tested for their ability to process and present native protein Ag in the presence of the protein synthesis inhibitor cycloheximide or the protein synthesis inhibitor cycloheximide or the protein export inhibitor, Brefeldin A. Both agents blocked the presentation of native OVA or native hen egg lysozyme to Ag-specific T cell hybridomas. No effect was seen on peptide presentation or on presentation to allo- or autoreactive T cells. Inasmuch as Brefeldin A has been previously shown to block protein export without affecting protein internalization or protein degradation in the endocytic pathway, the simplest interpretation of these data is that antigenic fragments generated in the APC after uptake by the endocytic pathway, preferentially associate with newly synthesized rather than mature MHC class II proteins.
蛋白质抗原与MHC II类蛋白的呈递过程包括通过内吞作用摄取蛋白质抗原，随后在细胞内酸性区室中进行加工，可能是蛋白水解。然而，关于在此过程中抗原和MHC II类蛋白所采取的精确途径仍存在相当大的争议。Ag-MHC II类蛋白复合物异常的稳定性导致推测抗原只能与新合成的MHC II类分子结合。另一种可能性是，在MHC II类蛋白内化和再循环过程中，细胞内可以再生MHC II类结合位点。为了探究这些可能性，测试了三种不同的小鼠B淋巴瘤细胞系在存在蛋白质合成抑制剂放线菌酮或蛋白质合成抑制剂放线菌酮或蛋白质输出抑制剂布雷菲德菌素A的情况下加工和呈递天然蛋白质抗原的能力。两种试剂均阻断了天然OVA或天然鸡蛋清溶菌酶向抗原特异性T细胞杂交瘤的呈递。对肽呈递或向同种异体或自身反应性T细胞的呈递没有影响。由于布雷菲德菌素A先前已被证明可阻断蛋白质输出，而不影响蛋白质内化或内吞途径中的蛋白质降解，这些数据最简单的解释是，抗原提呈细胞通过内吞途径摄取后产生的抗原片段优先与新合成的而非成熟的MHC II类蛋白结合。
