Role of lipid trimming and CD1 groove size in cellular antigen presentation.
Cellular CD1 proteins bind lipids that differ in length (C(12-80)), including antigens that exceed the capacity of the CD1 groove. This could be accomplished by trimming lipids to a uniform length before loading or by inserting each lipid so that it penetrates the groove to a varying extent. New assays to detect antigen fragments generated within human dendritic cells showed that bacterial antigens remained intact, even after delivery to lysosomes, where control lipids were cleaved. Further, recombinant CD1b proteins could bind and present C(80) lipid antigens using a mechanism that did not involve cellular enzymes or lipid cleavage, but was regulated by pH in the physiologic range. We conclude that endosomal acidification acts directly, rather than through enzymatic trimming, to insert lipids into CD1b. Lipids are loaded in an intact form, so that they likely protrude through a portal near the bottom of the groove, which represents an escape hatch for long lipids from mycobacterial pathogens.
Cheng
Tan-Yun
TY
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Relloso
Miguel
M
Van Rhijn
Ildiko
I
Young
David C
DC
Besra
Gurdyal S
GS
Briken
Volker
V
Zajonc
Dirk M
DM
Wilson
Ian A
IA
Porcelli
Steven
S
Moody
D Branch
DB
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D002474:Cell-Free System; D003713:Dendritic Cells / Q000276:immunology*; D011992:Endosomes / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; D008055:Lipids