title: Leishmania antigens are presented to CD8+ T cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo.
abstract: CD8+ T cells are generated in response to Leishmania major (Lm) or Toxoplasma gondii parasitic infections, indicating that exogenously delivered Ag can be processed for presentation by MHC class I molecules. We show that presentation of Lm nucleotidase (NT)-OVA is TAP independent in vivo and in vitro, and is inhibited by chloroquine, but not by proteasome inhibitors. In contrast, the presentation of T. gondii P30-OVA relies on the TAP/proteasome pathway. Presentation of OVA- or rNT-OVA-coated beads also bypassed TAP requirement above a certain Ag threshold. TAP was also dispensable for the presentation of wild-type Lm Ags to primed CD8+ T cells in vitro. Finally, in vivo priming of CD8+ T cells involved in acquired resistance to Lm was not compromised in TAP-deficient mice. Thus, Leishmania Ags appear to be confined to an intraphagosomal processing pathway that requires higher concentrations of Ags, suggesting that these parasites may have evolved strategies to impair the efficient endoplasmic reticulum-based, TAP-dependent cross-presentation pathway to avoid or delay CD8+ T cell priming.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.forename: Romina
authors.initials: R
authors.lastname: Goldszmid
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
authors.forename: Alain
authors.initials: A
authors.lastname: Debrabant
authors.forename: Farhat
authors.initials: F
authors.lastname: Afrin
authors.forename: Carmen
authors.initials: C
authors.lastname: Collazo-Custodio
authors.forename: Mathieu
authors.initials: M
authors.lastname: Houde
authors.forename: Michel
authors.initials: M
authors.lastname: Desjardins
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: David
authors.initials: D
authors.lastname: Sacks
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004527:Egg Proteins / Q000378:metabolism; D018320:Leishmania major / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D010446:Peptide Fragments; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000953:Antigens, Protozoan; D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; C486171:Tap1 protein, mouse; D010047:Ovalbumin