Buckner F S, Wipke B T, Van Voorhis W C
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, USA.
Eur J Immunol. 1997 Oct;27(10):2541-8. doi: 10.1002/eji.1830271012.
Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas' disease, lives free within the cytoplasm of infected host cells. This intracellular niche suggests that parasite antigens may be processed and presented on major histocompatibility complex (MHC) class I molecules for recognition by CD8+ T cells. However, the parasite persists indefinitely in the mammalian host, indicating its success at evading immune clearance. It has been shown that T. cruzi interferes with processing and presentation of antigenic peptides in the MHC class II pathway. This investigation sought to determine whether interference in MHC class I processing and presentation occurs with T. cruzi infection. Surface expression of MHC class I molecules was found to be unaffected or up-regulated by T. cruzi infection in vitro. A model system employing a beta-galactosidase (beta-gal)-specific murine cytotoxic T lymphocyte (CTL) line (0805B) showed: (i) in vitro infection of mouse peritoneal macrophages or J774 cells with T. cruzi did not inhibit MHC class I presentation of exogenous peptide (a nine-amino acid epitope of beta-gal) to the CTL line, (ii) in vitro infection of a beta-gal-expressing 3T3 cell line (LZEJ) with T. cruzi did not inhibit MHC class I presentation of the endogenous protein to the CTL line and (iii) mouse renal adenocarcinoma cells infected with T. cruzi and subsequently infected with adenovirus expressing beta-gal were able to present antigen to the beta-gal-specific CTL line. These findings indicate that the failure of the immune response to clear T. cruzi does not result from global interference by the parasite with MHC class I processing and presentation. Parasites engineered to express beta-gal were unable to sensitize infected antigen-presenting cells in vitro to lysis by the CTL 0805B line. This was probably due to the intracellular localization of the beta-gal within the parasite and its inaccessibility to the host cell cytoplasm.
克氏锥虫（T. cruzi）是恰加斯病的病原体，在受感染宿主细胞的细胞质中自由生存。这种细胞内生态位表明，寄生虫抗原可能会被加工并呈递到主要组织相容性复合体（MHC）I类分子上，以供CD8 + T细胞识别。然而，该寄生虫在哺乳动物宿主中会无限期持续存在，这表明其成功逃避了免疫清除。已有研究表明，克氏锥虫会干扰MHC II类途径中抗原肽的加工和呈递。本研究旨在确定克氏锥虫感染是否会干扰MHC I类加工和呈递。研究发现，体外克氏锥虫感染不会影响或上调MHC I类分子的表面表达。一个采用β-半乳糖苷酶（β-gal）特异性小鼠细胞毒性T淋巴细胞（CTL）系（0805B）的模型系统显示：（i）用克氏锥虫体外感染小鼠腹腔巨噬细胞或J774细胞不会抑制外源性肽（β-gal的九氨基酸表位）向CTL系的MHC I类呈递；（ii）用克氏锥虫体外感染表达β-gal的3T3细胞系（LZEJ）不会抑制内源性蛋白向CTL系的MHC I类呈递；（iii）用克氏锥虫感染并随后用表达β-gal的腺病毒感染的小鼠肾腺癌细胞能够将抗原呈递给β-gal特异性CTL系。这些发现表明，免疫反应无法清除克氏锥虫并非是由于寄生虫对MHC I类加工和呈递的全面干扰所致。经基因工程改造以表达β-gal的寄生虫在体外无法使受感染的抗原呈递细胞对CTL 0805B系的裂解敏感。这可能是由于β-gal在寄生虫内的细胞内定位及其无法进入宿主细胞质所致。
