Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns

Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide

Aaron A.R. Tobian, Nicholas S. Potter, Lakshmi Ramachandra, Rish Pai, Marilyn Convery, W. Henry Boom, Clifford V. Harding

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Pathogen-associated molecular patterns (PAMPs) signal through Toll-like receptors (TLRs) to activate immune responses, but prolonged exposure to PAMPs from Mycobacterium tuberculosis (MTB) and other pathogens inhibits class II MHC (MHC-II) expression and Ag processing, which may allow MTB to evade CD4+ T cell immunity. Alternate class I MHC (MHC-I) processing allows macrophages to present Ags from MTB and other bacteria to CD8+ T cells, but the effect of PAMPs on this processing pathway is unknown. In our studies, MTB and TLR-signaling PAMPs, MTB 19-kDa lipoprotein, CpG DNA, and LPS, inhibited alternate MHC-I processing of latex-conjugated Ag by IFN-γ-activated macrophages. Inhibition was dependent on TLR-2 for MTB 19-kDa lipoprotein (but not whole MTB or the other PAMPs); inhibition was dependent on myeloid differentiation factor 88 for MTB and all of the individual PAMPs. Inhibition of MHC-II and alternate MHC-I processing was delayed, appearing after 16 h of PAMP exposure, as would occur in chronically infected macrophages. Despite inhibition of alternate MHC-I Ag processing, there was no inhibition of MHC-I expression, MHC-I-restricted presentation of exogenous peptide or conventional MHC-I processing of cytosolic Ag. MTB 19-kDa lipoprotein and other PAMPs inhibited phagosome maturation and phagosome Ag degradation in a myeloid differentiation factor 88-dependent manner; this may limit availability of peptides to bind MHC-I. By inhibiting both MHC-II and alternate MHC-I Ag processing, pathogens that establish prolonged infection of macrophages (>16 h), e.g., MTB, may immunologically silence macrophages and evade surveillance by both CD4+ and CD8+ T cells, promoting chronic infection.

Original languageEnglish (US)
Pages (from-to)1413-1422
Number of pages10
JournalJournal of Immunology
Volume171
Issue number3
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class I
Toll-Like Receptors
Antigen Presentation
Mycobacterium tuberculosis
Lipoproteins
Lipopolysaccharides
DNA
Macrophages
Myeloid Differentiation Factor 88
Phagosomes
T-Lymphocytes
Pathogen-Associated Molecular Pattern Molecules
Toll-Like Receptor 2
Peptides
Latex
Infection
Immunity
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns : Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide. / Tobian, Aaron A.R.; Potter, Nicholas S.; Ramachandra, Lakshmi; Pai, Rish; Convery, Marilyn; Boom, W. Henry; Harding, Clifford V.

In: Journal of Immunology, Vol. 171, No. 3, 01.08.2003, p. 1413-1422.

Research output: Contribution to journalArticle

Tobian, Aaron A.R. ; Potter, Nicholas S. ; Ramachandra, Lakshmi ; Pai, Rish ; Convery, Marilyn ; Boom, W. Henry ; Harding, Clifford V. / Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns : Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide. In: Journal of Immunology. 2003 ; Vol. 171, No. 3. pp. 1413-1422.
@article{0f2753001efc449692b3ea761bd3940e,
title = "Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns: Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide",
abstract = "Pathogen-associated molecular patterns (PAMPs) signal through Toll-like receptors (TLRs) to activate immune responses, but prolonged exposure to PAMPs from Mycobacterium tuberculosis (MTB) and other pathogens inhibits class II MHC (MHC-II) expression and Ag processing, which may allow MTB to evade CD4+ T cell immunity. Alternate class I MHC (MHC-I) processing allows macrophages to present Ags from MTB and other bacteria to CD8+ T cells, but the effect of PAMPs on this processing pathway is unknown. In our studies, MTB and TLR-signaling PAMPs, MTB 19-kDa lipoprotein, CpG DNA, and LPS, inhibited alternate MHC-I processing of latex-conjugated Ag by IFN-γ-activated macrophages. Inhibition was dependent on TLR-2 for MTB 19-kDa lipoprotein (but not whole MTB or the other PAMPs); inhibition was dependent on myeloid differentiation factor 88 for MTB and all of the individual PAMPs. Inhibition of MHC-II and alternate MHC-I processing was delayed, appearing after 16 h of PAMP exposure, as would occur in chronically infected macrophages. Despite inhibition of alternate MHC-I Ag processing, there was no inhibition of MHC-I expression, MHC-I-restricted presentation of exogenous peptide or conventional MHC-I processing of cytosolic Ag. MTB 19-kDa lipoprotein and other PAMPs inhibited phagosome maturation and phagosome Ag degradation in a myeloid differentiation factor 88-dependent manner; this may limit availability of peptides to bind MHC-I. By inhibiting both MHC-II and alternate MHC-I Ag processing, pathogens that establish prolonged infection of macrophages (>16 h), e.g., MTB, may immunologically silence macrophages and evade surveillance by both CD4+ and CD8+ T cells, promoting chronic infection.",
author = "Tobian, {Aaron A.R.} and Potter, {Nicholas S.} and Lakshmi Ramachandra and Rish Pai and Marilyn Convery and Boom, {W. Henry} and Harding, {Clifford V.}",
year = "2003",
month = "8",
day = "1",
doi = "10.4049/jimmunol.171.3.1413",
language = "English (US)",
volume = "171",
pages = "1413--1422",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Alternate class I MHC antigen processing is inhibited by Toll-like receptor signaling pathogen-associated molecular patterns

T2 - Mycobacterium tuberculosis 19-kDa lipoprotein, CpG DNA, and lipopolysaccharide

AU - Tobian, Aaron A.R.

AU - Potter, Nicholas S.

AU - Ramachandra, Lakshmi

AU - Pai, Rish

AU - Convery, Marilyn

AU - Boom, W. Henry

AU - Harding, Clifford V.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Pathogen-associated molecular patterns (PAMPs) signal through Toll-like receptors (TLRs) to activate immune responses, but prolonged exposure to PAMPs from Mycobacterium tuberculosis (MTB) and other pathogens inhibits class II MHC (MHC-II) expression and Ag processing, which may allow MTB to evade CD4+ T cell immunity. Alternate class I MHC (MHC-I) processing allows macrophages to present Ags from MTB and other bacteria to CD8+ T cells, but the effect of PAMPs on this processing pathway is unknown. In our studies, MTB and TLR-signaling PAMPs, MTB 19-kDa lipoprotein, CpG DNA, and LPS, inhibited alternate MHC-I processing of latex-conjugated Ag by IFN-γ-activated macrophages. Inhibition was dependent on TLR-2 for MTB 19-kDa lipoprotein (but not whole MTB or the other PAMPs); inhibition was dependent on myeloid differentiation factor 88 for MTB and all of the individual PAMPs. Inhibition of MHC-II and alternate MHC-I processing was delayed, appearing after 16 h of PAMP exposure, as would occur in chronically infected macrophages. Despite inhibition of alternate MHC-I Ag processing, there was no inhibition of MHC-I expression, MHC-I-restricted presentation of exogenous peptide or conventional MHC-I processing of cytosolic Ag. MTB 19-kDa lipoprotein and other PAMPs inhibited phagosome maturation and phagosome Ag degradation in a myeloid differentiation factor 88-dependent manner; this may limit availability of peptides to bind MHC-I. By inhibiting both MHC-II and alternate MHC-I Ag processing, pathogens that establish prolonged infection of macrophages (>16 h), e.g., MTB, may immunologically silence macrophages and evade surveillance by both CD4+ and CD8+ T cells, promoting chronic infection.

AB - Pathogen-associated molecular patterns (PAMPs) signal through Toll-like receptors (TLRs) to activate immune responses, but prolonged exposure to PAMPs from Mycobacterium tuberculosis (MTB) and other pathogens inhibits class II MHC (MHC-II) expression and Ag processing, which may allow MTB to evade CD4+ T cell immunity. Alternate class I MHC (MHC-I) processing allows macrophages to present Ags from MTB and other bacteria to CD8+ T cells, but the effect of PAMPs on this processing pathway is unknown. In our studies, MTB and TLR-signaling PAMPs, MTB 19-kDa lipoprotein, CpG DNA, and LPS, inhibited alternate MHC-I processing of latex-conjugated Ag by IFN-γ-activated macrophages. Inhibition was dependent on TLR-2 for MTB 19-kDa lipoprotein (but not whole MTB or the other PAMPs); inhibition was dependent on myeloid differentiation factor 88 for MTB and all of the individual PAMPs. Inhibition of MHC-II and alternate MHC-I processing was delayed, appearing after 16 h of PAMP exposure, as would occur in chronically infected macrophages. Despite inhibition of alternate MHC-I Ag processing, there was no inhibition of MHC-I expression, MHC-I-restricted presentation of exogenous peptide or conventional MHC-I processing of cytosolic Ag. MTB 19-kDa lipoprotein and other PAMPs inhibited phagosome maturation and phagosome Ag degradation in a myeloid differentiation factor 88-dependent manner; this may limit availability of peptides to bind MHC-I. By inhibiting both MHC-II and alternate MHC-I Ag processing, pathogens that establish prolonged infection of macrophages (>16 h), e.g., MTB, may immunologically silence macrophages and evade surveillance by both CD4+ and CD8+ T cells, promoting chronic infection.

UR - http://www.scopus.com/inward/record.url?scp=0041344387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041344387&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.171.3.1413

DO - 10.4049/jimmunol.171.3.1413

M3 - Article

VL - 171

SP - 1413

EP - 1422

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -