Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells
Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells
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DOI：
10.1073/pnas.0502255102
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发表时间：
2005-05-31
影响因子：
11.1
通讯作者：
Unanue, ER
中科院分区：
文献类型：
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作者：
Herzog, J;Maekawa, Y;Unanue, ER
CD4T细胞识别翻译后修饰的蛋白蛋白溶菌酶（HEL）肽，包括酪氨酸的硝化和T细胞接触残基中色氨酸的修饰。T细胞直接针对化学上占优势的HEL肽的修饰，以及与II类组织相容性分子I-A(k)结合的次要HEL肽。这些修饰肽可以在体内用天然HEL分子免疫后生成，也可以在体外用过氧亚硝酸盐处理HEL生成。此外，抗原呈递细胞（APC），无论是在培养或体内激活的巨噬细胞还是树突状细胞，都会产生修饰的HEL表位，刺激T细胞。在表达HEL的转基因小鼠中，修饰表位上的T细胞逃脱了负选择，并被发现，尽管数量少于正常小鼠。单核细胞增生李斯特菌感染转基因HEL小鼠产生含有修饰的AIPC。APC活化诱导T细胞到修饰的表位可能是抗微生物免疫和自身免疫反应的一个组成部分。
CD4T cells recognized posttranslationally modified peptides of the protein hen egg-white lysozyme (HEL), consisting of nitration of tyrosines and modifications of tryptophans in the T cell contact residues of the peptides. T cells were directed against modifications of a chemically dominant HEL peptide as well as a minor HEL peptide, bound to the class II histocompatibility molecule I-A(k). The modified peptides were generated in vivo after immunization with native HEL molecules or were generated ex vivo by peroxynitrite treatment of HEL. Moreover, antigen-presenting cells (APC), either macrophages or dendritic cells activated in culture or in vivo, generated the modified HEL epitopes that stimulated the T cells. In transgenic mice expressing HEL, the T cells to the modified epitopes escaped negative selection and were found, albeit fewer in number than in normal mice. Infection with Listeria monocytogenes of the transgenic HEL mice generated AIPC containing the modifications. T cells to modified epitopes induced by activation of APC may be a component of antimicrobial immunity and autoimmune reactions.