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J Immunol 2006 Sep 15;177(6):3525-33

Leishmania antigens are presented to CD8+ T Cells by a transporter associated with antigen processing-independent pathway in vitro and in vivo.

Bertholet S, Goldszmid R, Morrot A, Debrabant A, Afrin F, Collazo-Custodio C, Houde M, Desjardins M, Sher A, Sacks D

Sacks D, NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ, Canada

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.


Category: Journal Article
PubMed ID: #16951311
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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