PMID- 12874233
OWN - NLM
STAT- MEDLINE
DCOM- 20031107
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 171
IP  - 3
DP  - 2003 Aug 1
TI  - 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.
PG  - 1413-22
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-gamma-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.
FAU - Tobian, Aaron A R
AU  - Tobian AA
AD  - Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, 
      USA.
FAU - Potter, Nicholas S
AU  - Potter NS
FAU - Ramachandra, Lakshmi
AU  - Ramachandra L
FAU - Pai, Rish K
AU  - Pai RK
FAU - Convery, Marilyn
AU  - Convery M
FAU - Boom, W Henry
AU  - Boom WH
FAU - Harding, Clifford V
AU  - Harding CV
LA  - eng
GR  - AI27243/AI/NIAID NIH HHS/United States
GR  - AI34343/AI/NIAID NIH HHS/United States
GR  - AI35726/AI/NIAID NIH HHS/United States
GR  - AI47225/AI/NIAID NIH HHS/United States
GR  - AI95383/AI/NIAID NIH HHS/United States
GR  - HL55967/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (19 kDa antigen, Mycobacterium)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lipoproteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigen Presentation/*immunology
MH  - Antigens, Differentiation/physiology
MH  - Bacterial Proteins/*physiology
MH  - Cell Differentiation/immunology
MH  - Cell Fractionation
MH  - Cells, Cultured
MH  - CpG Islands/*immunology
MH  - Down-Regulation/immunology
MH  - Female
MH  - Histocompatibility Antigens Class I/biosynthesis/*immunology/metabolism
MH  - Histocompatibility Antigens Class II/biosynthesis/immunology
MH  - Immunosuppressive Agents/pharmacology
MH  - Lipopolysaccharides/*immunology
MH  - Lipoproteins/physiology
MH  - Macrophages/cytology/immunology/metabolism/microbiology
MH  - Membrane Glycoproteins/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Knockout
MH  - Mycobacterium tuberculosis/chemistry/*immunology
MH  - Myeloid Differentiation Factor 88
MH  - Peptides/immunology/metabolism
MH  - Phagocytosis/immunology
MH  - Phagosomes/immunology/metabolism/microbiology
MH  - Receptors, Cell Surface/*physiology
MH  - Receptors, Immunologic/physiology
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptors
EDAT- 2003/07/23 05:00
MHDA- 2003/11/08 05:00
CRDT- 2003/07/23 05:00
PHST- 2003/07/23 05:00 [pubmed]
PHST- 2003/11/08 05:00 [medline]
PHST- 2003/07/23 05:00 [entrez]
AID - 10.4049/jimmunol.171.3.1413 [doi]
PST - ppublish
SO  - J Immunol. 2003 Aug 1;171(3):1413-22. doi: 10.4049/jimmunol.171.3.1413.