The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CD1b molecules

Theodore I. Prigozy; Peter A. Sieling; Daniel Clemens; Phoebe L. Stewart; Samuel M. Behar; Steven A. Porcelli; Michael B. Brenner; Robert L. Modlin; Mitchell Kronenberg

doi:10.1016/S1074-7613(00)80425-2

The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CD1b molecules

Theodore I. Prigozy, Peter A. Sieling, Daniel Clemens, Phoebe L. Stewart, Samuel M. Behar, Steven A. Porcelli, Michael B. Brenner, Robert L. Modlin, Mitchell Kronenberg

Research output: Contribution to journal › Article › peer-review

303 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	187-197
Number of pages	11
Journal	Immunity
Volume	6
Issue number	2
DOIs	https://doi.org/10.1016/S1074-7613(00)80425-2
State	Published - Feb 1997
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S1074-7613(00)80425-2

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title = "The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CD1b molecules",

abstract = "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.",

author = "Prigozy, {Theodore I.} and Sieling, {Peter A.} and Daniel Clemens and Stewart, {Phoebe L.} and Behar, {Samuel M.} and Porcelli, {Steven A.} and Brenner, {Michael B.} and Modlin, {Robert L.} and Mitchell Kronenberg",

note = "Funding Information: Correspondence should be addressed to M. K. The authors wish to thank Dr. Philip Stahl and Dr. Frances Brodsky for the anti-MR antiserum and the AP6 monoclonal antibody, respectively. We gratefully acknowledge Paul Singh and Jeff Chun for processing of the confocal images. We thank Dr. Patrick Brennan and Dr. Delphi Chatterjee for providing purified LAM for these studies. This work was supported by National Institutes of Health (NIH) grants CA52511 (M. K.), AR 40312 (R. L. M.), and AI 35275 (D. C.); T. I. P. was supported by NIH training grant AI 07126-19.",

year = "1997",

month = feb,

doi = "10.1016/S1074-7613(00)80425-2",

language = "English (US)",

volume = "6",

pages = "187--197",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CD1b molecules

AU - Prigozy, Theodore I.

AU - Sieling, Peter A.

AU - Clemens, Daniel

AU - Stewart, Phoebe L.

AU - Behar, Samuel M.

AU - Porcelli, Steven A.

AU - Brenner, Michael B.

AU - Modlin, Robert L.

AU - Kronenberg, Mitchell

N1 - Funding Information: Correspondence should be addressed to M. K. The authors wish to thank Dr. Philip Stahl and Dr. Frances Brodsky for the anti-MR antiserum and the AP6 monoclonal antibody, respectively. We gratefully acknowledge Paul Singh and Jeff Chun for processing of the confocal images. We thank Dr. Patrick Brennan and Dr. Delphi Chatterjee for providing purified LAM for these studies. This work was supported by National Institutes of Health (NIH) grants CA52511 (M. K.), AR 40312 (R. L. M.), and AI 35275 (D. C.); T. I. P. was supported by NIH training grant AI 07126-19.

PY - 1997/2

Y1 - 1997/2

N2 - 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.

AB - 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.

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JO - Immunity

JF - Immunity

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ER -

The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CD1b molecules

Abstract

ASJC Scopus subject areas

UN SDGs

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