Casten L A, Pierce S K
Department of Biochemistry, Northewestern University, Evanston, IL 60208.
J Immunol. 1988 Jan 15;140(2):404-10.
Helper T cell recognition of globular protein antigens requires the intracellular processing of the native molecule by an antigen-presenting cell and subsequent presentation of a peptide fragment, containing the antigenic determinant, on the cell surface where it is recognized by the specific T cell in conjunction with Ia. B lymphocytes can function as antigen-presenting cells and, when antigen is bound by their surface Ig, are greatly enhanced in this capacity. In this report it is demonstrated that pigeon cytochrome c covalently coupled to antibodies directed toward either B cell surface immunoglobulin, class I or class II are effectively processed and presented by B cells to cytochrome c-specific T cells, requiring up to 1000-fold less cytochrome c as compared with cytochrome c alone or cytochrome c coupled to nonspecific immunoglobulin. The potent activity of the cytochrome c-antibody conjugates appears to be due to the ability of B cells to concentrate the antigen when the process becomes receptor mediated rather than to a signal provided to the B cell by the conjugate binding, because cytochrome c was not more effectively presented in the presence of unconjugated antibodies as compared with cytochrome c alone. Furthermore, the binding of the native antigen to B cell surfaces is not alone sufficient for T cell activation, in that the cytochrome c-antibody conjugates require processing and are major histocompatibility complex restricted. The results presented here indicate that surface immunoglobulin is not unique in its ability to facilitate antigen processing and/or presentation and that Ig, class I and class II are capable of transporting the cytochrome c to a cytoplasmic vesicle where proteolysis occurs yielding the required peptide, minimally of 10 amino acids. Cytochrome c coupled to monovalent fragments of anti-Ig-antibodies was nearly as effectively presented as cytochrome c coupled to bivalent antibodies, indicating that phenomena mediated by bivalent binding, such as patching and capping of the surface Ig, were not required for effective antigen presentation. The cytochrome c-antibody conjugates, which allow antigen processing to be initiated by receptor-mediated endocytosis, may provide the necessary tools to unravel the intracellular processes by which protein antigens are processed and presented by B lymphocytes.
辅助性T细胞对球状蛋白抗原的识别需要抗原呈递细胞对天然分子进行细胞内加工，随后在细胞表面呈递含有抗原决定簇的肽片段，在此处它与Ia一起被特异性T细胞识别。B淋巴细胞可作为抗原呈递细胞，当抗原被其表面免疫球蛋白结合时，其这种能力会大大增强。在本报告中，证明了与针对B细胞表面免疫球蛋白、I类或II类的抗体共价偶联的鸽细胞色素c能被B细胞有效地加工并呈递给细胞色素c特异性T细胞，与单独的细胞色素c或与非特异性免疫球蛋白偶联的细胞色素c相比，所需的细胞色素c量减少多达1000倍。细胞色素c-抗体偶联物的强大活性似乎是由于当该过程变为受体介导时B细胞浓缩抗原的能力，而不是由于偶联物结合向B细胞提供的信号，因为与单独的细胞色素c相比，在未偶联抗体存在的情况下细胞色素c并没有更有效地呈递。此外，天然抗原与B细胞表面的结合本身不足以激活T细胞，因为细胞色素c-抗体偶联物需要加工且受主要组织相容性复合体限制。此处给出的结果表明，表面免疫球蛋白在促进抗原加工和/或呈递的能力方面并非独一无二，并且Ig、I类和II类能够将细胞色素c转运至细胞质囊泡，在那里发生蛋白水解产生所需的肽，最少为10个氨基酸。与抗Ig抗体的单价片段偶联的细胞色素c几乎与与二价抗体偶联的细胞色素c一样有效地呈递，这表明有效抗原呈递不需要由二价结合介导的现象，如表面Ig的贴片和封帽。细胞色素c-抗体偶联物允许通过受体介导的内吞作用启动抗原加工，可能提供必要的工具来阐明蛋白质抗原被B淋巴细胞加工和呈递的细胞内过程。
