Trypanosoma cruzi infection does not impair major histocompatibility complex class I presentation of antigen to cytotoxic T lymphocytes.
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.
Buckner
F S
FS
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, USA. fbuckner@u.washington.edu
Wipke
B T
BT
Van Voorhis
W C
WC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D001616:beta-Galactosidase / Q000378:metabolism
D006183:H-2 Antigens; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D001616:beta-Galactosidase