Schoenberger S P, van der Voort E I, Krietemeijer G M, Offringa R, Melief C J, Toes R E
Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
J Immunol. 1998 Oct 15;161(8):3808-12.
It has been proposed that the cross-priming of CTL responses in vivo involves the transfer to host APCs of heat shock protein glycoprotein 96-chaperoned antigenic peptides released from the endoplasmic reticulum (ER) of dying or infected cells. We have tested this possibility directly using TAP-deficient cell lines lacking antigenic ER peptides derived from two model Ags, the human adenovirus type 5 early regions E1A and E1B. Although both proteins were well expressed, the cells were not recognized by E1A- or E1B-specific CTLs unless the relevant epitope was either provided exogenously as a synthetic peptide or targeted to the ER in a TAP-independent fashion. Despite the absence of these ER peptides, the TAP1-/- cells were able to efficiently cross-prime E1A- and E1B-specific CTLs following immunization of syngeneic mice. These results indicate that, although purified peptide/glycoprotein 96 complexes are potent immunogens, the mechanism of CTL cross-priming in vivo does not depend upon antigenic peptides in the ER of immunizing cells.
有人提出，体内CTL反应的交叉呈递涉及从垂死或受感染细胞的内质网（ER）释放的热休克蛋白糖蛋白96伴侣抗原肽转移至宿主抗原呈递细胞（APC）。我们使用缺乏源自两种模式抗原（人5型腺病毒早期区域E1A和E1B）的抗原性ER肽的TAP缺陷细胞系直接测试了这种可能性。尽管两种蛋白均表达良好，但除非相关表位以合成肽的形式外源提供或以不依赖TAP的方式靶向内质网，否则这些细胞不会被E1A或E1B特异性CTL识别。尽管缺乏这些ER肽，但在同基因小鼠免疫后，TAP1-/-细胞能够有效地交叉呈递E1A和E1B特异性CTL。这些结果表明，尽管纯化的肽/糖蛋白96复合物是有效的免疫原，但体内CTL交叉呈递的机制并不依赖于免疫细胞内质网中的抗原肽。
