PMID- 11938350 OWN - NLM STAT- MEDLINE DCOM- 20020531 LR - 20220227 IS - 1529-2908 (Print) IS - 1529-2908 (Linking) VI - 3 IP - 5 DP - 2002 May TI - Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation. PG - 435-42 AB - 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. FAU - Moody, D Branch AU - Moody DB AD - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. bmoody@rics.bwh.harvard.edu FAU - Briken, Volker AU - Briken V FAU - Cheng, Tan-Yun AU - Cheng TY FAU - Roura-Mir, Carme AU - Roura-Mir C FAU - Guy, Mark R AU - Guy MR FAU - Geho, David H AU - Geho DH FAU - Tykocinski, Mark L AU - Tykocinski ML FAU - Besra, Gurdyal S AU - Besra GS FAU - Porcelli, Steven A AU - Porcelli SA LA - eng GR - AI 31044/AI/NIAID NIH HHS/United States GR - AI 38960/AI/NIAID NIH HHS/United States GR - AI45889/AI/NIAID NIH HHS/United States GR - AI48933/AI/NIAID NIH HHS/United States GR - AI49313/AI/NIAID NIH HHS/United States GR - ARO1988/AR/NIAMS NIH HHS/United States GR - CA74958/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20020408 PL - United States TA - Nat Immunol JT - Nature immunology JID - 100941354 RN - 0 (Antigens, CD1) RN - 0 (CD1b antigen) RN - 0 (Glycolipids) RN - 0 (Interleukin-2) RN - 0 (glucose mycolate) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) SB - IM CIN - Nat Immunol. 2002 May;3(5):421-2. PMID: 11976717 MH - Antigen Presentation/*immunology MH - Antigens, CD1/*immunology MH - Dendritic Cells/immunology/metabolism MH - Endosomes/*immunology/metabolism MH - Glycolipids/*immunology MH - Humans MH - Interleukin-2/analysis/biosynthesis MH - Lysosomes/immunology MH - Structure-Activity Relationship MH - T-Lymphocytes/immunology MH - Tumor Cells, Cultured MH - beta-N-Acetylhexosaminidases/analysis/biosynthesis EDAT- 2002/04/09 10:00 MHDA- 2002/06/01 10:01 CRDT- 2002/04/09 10:00 PHST- 2002/04/09 10:00 [pubmed] PHST- 2002/06/01 10:01 [medline] PHST- 2002/04/09 10:00 [entrez] AID - ni780 [pii] AID - 10.1038/ni780 [doi] PST - ppublish SO - Nat Immunol. 2002 May;3(5):435-42. doi: 10.1038/ni780. Epub 2002 Apr 8.