The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CD1b molecules.
We have characterized the CD1b-mediated presentation pathway for the mycobacterial lipoglycan lipoarabinomannan (LAM) in monocyte-derived antigen-presenting cells. The macrophage mannose receptor (MR) was responsible for uptake of LAM. Antagonism of MR function inhibited both the internalization of LAM and the presentation of this antigen to LAM-reactive T cells. Intracellular MRs were most abundant in early endosomes, but they also were located in the compartment for MHC class II antigen loading (MIIC). Internalized LAM was transported to late endosomes, lysosomes, and MIICs. MRs colocalized with CD1b molecules, suggesting that the MR could deliver LAM to late endosomes for loading onto CD1b. LAM and CD1b colocalized in organelles that may be sites of lipoglycan antigen loading. This pathway links recognition of microbial antigens by a receptor of the innate immune system to the induction of adaptive T cell responses.
Prigozy
T I
TI
Department of Microbiology and Immunology, University of California at Los Angeles 90095, USA.
Sieling
P A
PA
Clemens
D
D
Stewart
P L
PL
Behar
S M
SM
Porcelli
S A
SA
Brenner
M B
MB
Modlin
R L
RL
Kronenberg
M
M
D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D018949:Antigens, CD1 / Q000235:genetics*; D001692:Biological Transport / Q000502:physiology; D011992:Endosomes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000276:immunology* / Q000493:pharmacokinetics*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009166:Mycobacterium leprae / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C050016:lipoarabinomannan