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 β‐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. mexicanagal induces β‐galactosidase‐specific cytotoxic T cells (CTL), which can be isolated using a β‐galactosidase‐expressing mastocytoma line as an antigen‐presenting cell. These CTL recognize epitopes of β‐galactosidase in the context of H‐2K^d; however, they do not recognize L. mexicanagal‐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.