Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation.
CD1 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 CD1b 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 CD1b 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.
Moody
D Branch
DB
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. bmoody@rics.bwh.harvard.edu
Briken
Volker
V
Cheng
Tan-Yun
TY
Roura-Mir
Carme
C
Guy
Mark R
MR
Geho
David H
DH
Tykocinski
Mark L
ML
Besra
Gurdyal S
GS
Porcelli
Steven A
SA
D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000276:immunology* / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis; D008247:Lysosomes / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis / Q000096:biosynthesis
D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; D007376:Interleukin-2; C048938:glucose mycolate; D001619:beta-N-Acetylhexosaminidases