Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0232605 (regurgitation)
 8,217 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presentation of peptides derived from endogenous proteins on class I molecules needs functional TAP peptide transporters. To reveal whether class I-associated presentation of exogenous proteins also required the presence of TAP transporters, we assessed in vitro the ability of spleen cells and macrophages from TAP1-deficient mice (TAP1-/-) to present peptides derived from exogenous recombinant viral proteins on their class I molecules. We found that recombinant glyco- and nucleoprotein from lymphocytic choriomeningitis virus and nucleoprotein of vesicular stomatitis virus were presented as efficiently by TAP1-/- cells as by control cells. Peptide regurgitation was not involved. Since particulate, non-replicating antigens can efficiently prime anti-viral cytotoxic T cells in vivo, this new, TAP-independent pathway of class I-associated antigen presentation may be applicable for vaccine strategies.
 ...
PMID:TAP1-independent loading of class I molecules by exogenous viral proteins. 761 1

Latex-OVA and bacteria expressing an OVA fusion protein were processed by macrophages via an alternate class I MHC (MHC-I) processing pathway to present OVA(257-264):Kb. This pathway was resistant to dipeptide aldehyde proteasome inhibitors and brefeldin A, unlike the cytosolic MHC-I pathway. TAP1-/- macrophages exhibited decreases in cell surface peptide-receptive MHC-I and binding of extracellular peptide during transient incubations. This may explain an apparent influence of TAP on alternate MHC-I processing. Alternate MHC-I processing by TAP1-/- cells was enhanced by preincubation at 26 degrees C or with beta 2-microglobulin to increase peptide-receptive MHC-I. Thus, peptides may bind to MHC-I within post-Golgi vacuolar organelles accessible to exogenous beta 2-microglobulin or on the cell surface (following peptide regurgitation).
 ...
PMID:Roles of proteasomes, transporter for antigen presentation (TAP), and beta 2-microglobulin in the processing of bacterial or particulate antigens via an alternate class I MHC processing pathway. 866 86

Dendritic cells (DC) expanded in the presence of GM-CSF from the bone marrow of C57BL/6 mice process Gram-negative bacteria expressing the model antigen Crl-OVA for peptide presentation on MHC class I molecules. Here we show that presentation of OVA(257-264) processed by DC co-incubated with E. coli expressing Crl-OVA, which contains the Kb-binding OVA(257-264) epitope, occurs by a cytosolic MHC-I presentation pathway. First, we demonstrate the requirement for the transporter associated with antigen processing (TAP) by showing that DC from TAP1-/- mice co-incubated with E. coli expressing Crl-OVA did not result in Kb presentation of OVA(257-264). Second, the proteasome inhibitor MG132 abrogated presentation of OVA(257-264) on Kb when C57BL/6 DC phagocytosed and processed E. coli expressing Crl-OVA. Third, inhibiting protein synthesis using cycloheximide or blocking exocytosis of newly synthesized proteins from the endoplasmic reticulum using brefeldin A abrogated presentation of OVA(257-264) processed from bacteria expressing Crl-OVA by C57BL/6 DC. Finally, peptide regurgitation and loading of OVA(257-264) on neighboring bystander Kb-expressing antigen-presenting cells after BALB/c (H-2d) DC phagocytosed E. coli expressing Crl-OVA could not be detected. Together, these data support a cytosolic MHC-I presentation pathway for OVA(257-264) processed from E. coli expressing Crl-OVA by bone marrow-derived DC.
 ...
PMID:Classical MHC class I peptide presentation of a bacterial fusion protein by bone marrow-derived dendritic cells. 993 99