Leishmania mexicana promastigotes induce cytotoxic T lymphocytes in vivo that do not recognize infected macrophages.
The question is addressed whether antigens of Leishmania, a parasite residing in the endosomal compartment of macrophages, can be presented in the context of major histocompatibility complex class I molecules. We used E. coli beta-galactosidase as a model antigen which can be expressed in high levels in L. mexicana promastigotes (L. mexicana-gal). Infection of BALB/c mice with L. mexicana-gal induces beta-galactosidase-specific cytotoxic T cells (CTL), which can be isolated using a beta-galactosidase-expressing mastocytoma line as an antigen-presenting cell. These CTL recognize epitopes of beta-galactosidase in the context of H-2Kd; however, they do not recognize L. mexicana-gal-infected macrophages even after killing of the intracellular amastigotes by drug treatment or macrophage activation by lymphokines, although class I-peptide interaction and the presentation of endogenously produced antigens is normal. It is concluded that parasite antigens can induce a CTL response in vivo but that these CTL cannot recognize infected macrophages because the relevant epitopes cannot gain access to class I molecules. The effect of priming in vivo may be explained by the well-known but ill-understood phenomenon of cross-priming.
López
J A
JA
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
LeBowitz
J H
JH
Beverley
S M
SM
Rammensee
H G
HG
Overath
P
P
D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008815:Mice, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D001616:beta-Galactosidase