LEISHMANIA-MEXICANA PROMASTIGOTES INDUCE CYTOTOXIC LYMPHOCYTES-T INVIVO 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-2K(d); 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.