MHC class I-restricted presentation of maleylated protein binding to scavenger receptors.
Pathways for loading exogenous protein-derived peptides on MHC class I are thought to be present mainly in monocyte-lineage cells and to involve phagocytosis- or macropinocytosis-mediated antigenic leakage into either cytosol or extracellular milieu to give peptide access to MHC class I. We show that maleylation of OVA enhanced its presentation to an OVA-specific MHC class I-restricted T cell line by both macrophages and B cells. This enhanced presentation involved uptake through receptors of scavenger receptor (SR)-like ligand specificity, was TAP-1-independent, and was inhibited by low levels (2 mM) of ammonium chloride. No peptide loading of bystander APCs by maleylated (maleyl) OVA-pulsed macrophages was detected. Demaleylated maleyl-OVA showed enhanced MHC class I-restricted presentation through receptor-mediated uptake and remained highly sensitive to 2 mM ammonium chloride. However, if receptor binding of maleyl-OVA was inhibited by maleylated BSA, the residual presentation was relatively resistant to 2 mM ammonium chloride. Maleyl-OVA directly introduced into the cytosol via osmotic lysis of pinosomes was poorly presented, confirming that receptor-mediated presentation of exogenous maleyl-OVA was unlikely to involve a cytosolic pathway. Demaleylated maleyl-OVA was well presented as a cytosolic Ag, consistent with the dependence of cytosolic processing on protein ubiquitination. Thus, receptor-specific delivery of exogenous protein Ags to APCs can result in enhanced MHC class I-restricted presentation, suggesting that the exogenous pathway of peptide loading for MHC class I may be a constitutive property dependent mainly on the quantity of Ag taken up by APCs.
Bansal
P
P
National Institute of Immunology, New Delhi, India.
Mukherjee
P
P
Basu
S K
SK
George
A
A
Bal
V
V
Rath
S
S
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D011992:Endosomes / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008298:Maleates / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008298:Maleates; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C049877:maleylalbumin; D000643:Ammonium Chloride; D012710:Serum Albumin, Bovine; D010047:Ovalbumin; C030272:maleic acid