Antigen presentation by Leishmania mexicana-infected macrophages: activation of helper T cells specific for amastigote cysteine proteinases requires intracellular killing of the parasites.
Leishmania mexicana amastigotes proliferate in the phagolysosomes of mammalian macrophages. The parasites abundantly synthesize lysosomal cysteine proteinases, which are encoded by the lmcpb gene family. One of these genes was overexpressed in Escherichia coli, and the purified recombinant protein was used as an antigen to induce and establish a T helper 1 (Th1) cell line. The T cells recognize epitopes shared by the native cysteine proteinases and the recombinant protein. Infected bone marrow-derived macrophages induced to express major histocompatibility complex class II molecules by interferon (IFN)-gamma do not affect parasite viability. These macrophages fail to stimulate the proliferation of the T cell line. In contrast, strong T cell stimulation is observed after the parasites are killed by treatment with L-leucine methylester, or after activation of macrophages by IFN-gamma and tumor necrosis factor-alpha. It is concluded that infected macrophages efficiently present this lysosomal Leishmania antigen once the parasites are inactivated and degraded. This observation may be of considerable relevance for the outcome of Leishmania infections provided that it can be extended to other parasite antigens.
Wolfram
M
M
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Germany.
Ilg
T
T
Mottram
J C
JC
Overath
P
P
D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000276:immunology*; D018076:DNA, Complementary; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000953:Antigens, Protozoan; D018076:DNA, Complementary; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases