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Lipid length controls antigen entry into endosomal and nonendosomal pathways for CDIb presentation

Lookup NU author(s): Mark Guy, Professor Del Besra

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Abstract

CD I proteins present various glycolipid antigens to T cells, but the cellular mechanisms that control which particular glycolipids generate T cell responses are not understood. We show here that T cell recognition of glucose monomycolate antigens with long (C-80) alkyl chains involves the delivery of CD Ib proteins and antigens to late endosomes in a process that takes several hours. In contrast, analogs of the same antigen with shorter (C-32) alkyl chains are rapidly, but inefficiently, presented by cell surface CD Ib proteins. Dendritic cells (DCs) preferentially present long-chain glycolipids, which results, in part, from their rapid internalization and selective delivery of antigens to endosomal compartments. Nonprofessional antigen-presenting cells, however, preferentially present short-chain glycolipids because of their lack of prominent endosomal presentation pathways. Because long alkyl chain length distinguishes certain microbial glycolipids from common mammalian glycolipids, these findings suggest that DCs use a specialized endosomal-loading pathway to promote preferential recognition of glycolipids with a more intrinsically foreign structure.

Publication metadata

Author(s): Moody DB, Briken V, Cheng TY, Roura-Mir C, Guy MR, Geho DH, Tykocinski ML, Besra GS, Porcelli SA

Publication type: Article

Publication status: Published

Journal: Nature Immunology

Year: 2002

Volume: 3

Issue: 5

Pages: 435-442

ISSN (print): 1529-2908

ISSN (electronic): 1529-2916

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ni780

DOI: 10.1038/ni780

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