title: Presentation of the Leishmania antigen LACK by infected macrophages is dependent upon the virulence of the phagocytosed parasites.
abstract: We have previously demonstrated that murine macrophages (Mphi) infected with Leishmania promastigotes, in contrast to Mphi infected with the amastigote stage of these parasites, are able to present the Leishmania antigen LACK (Leishmania homologue of receptors for activated C kinase) to specific, I-Ad-restricted T cell hybrids and to the T cell clone 9.1-2. These T cells react with the LACK (158-173) peptide, which is immunodominant in BALB/c mice. Here, we show that the level of stimulation of the LACK-specific T cell hybridoma OD12 by promastigote-infected Mphi is clearly dependent upon the differentiation state of the internalized parasites. Thus, shortly after infection with log-phase or stationary-phase promastigotes of L. major or of L. amazonensis, Mphi strongly activated OD12. The activity was transient and rapidly lost. However, under the same conditions, activation of OD12 by Mphi infected with metacyclic promastigotes of L. major or of L. amazonensis was barely detectable. At the extreme, Mphi infected with amastigotes were incapable to stimulate OD12. Thus, the presentation of LACK by infected Mphi correlates with the degree of virulence of the phagocytosed parasites, the less virulent being the best for the generation/expression of LACK (158-173)-I-Ad complexes. While the intracellular killing of the parasites appears to be an important condition for the presentation of LACK, it is not the only requisite. The partial or total destruction of intracellular L. amazonensis amastigotes does not allow the presentation of LACK to OD12. A preferential interaction of LACK (158-173) with recycling rather than newly synthesized MHC class II molecules does not explain the transient presentation of LACK by Mphi infected with log-phase or stationary-phase promastigotes because brefeldin A strongly inhibited the presentation of LACK to OD12. Taken together, these results suggest that virulent stages of Leishmania, namely metacyclics and amastigotes, have evolved strategies to avoid or minimize their recognition by CD4+ T lymphocytes.
authors: Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur, Paris, France.
authors: N
authors: N
authors: Courret
authors: E
authors: E
authors: Prina
authors: E
authors: E
authors: Mougneau
authors: E M
authors: EM
authors: Saraiva
authors: D L
authors: DL
authors: Sacks
authors: N
authors: N
authors: Glaichenhaus
authors: J C
authors: JC
authors: Antoine
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D020126:Brefeldin A / Q000494:pharmacology; D005260:Female; D007891:Leishmania / Q000276:immunology / Q000472:pathogenicity*; D018320:Leishmania major / Q000276:immunology / Q000472:pathogenicity*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010587:Phagocytosis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015800:Protozoan Proteins / Q000276:immunology*; D014774:Virulence
chemical_list: D000953:Antigens, Protozoan; D011500:Protein Synthesis Inhibitors; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D020126:Brefeldin A