title: Modulation of T cell cytokine profiles and peptide-MHC complex availability in vivo by delivery to scavenger receptors via antigen maleylation.
abstract: We have previously shown that conversion of proteins to scavenger receptor (SR) ligands by maleylation increases their immunogenicity. We now show that maleyl-Ag-immune spleen cells make relatively more IFN-gamma and less IL-4 or IL-10 than native Ag-immune cells. This is also reflected in the IgG1:IgG2a ratios in Abs generated in vivo. SR engagement on macrophages does not alter their surface levels of the adhesive/costimulatory molecules CD11a/CD18, CD11b/CD18, CD24, CD54, or CD40, nor does it enhance their ability to support anti-CD3-driven proliferation of naive T cells in vitro. Costimulatory molecules implicated in differential Th1/Th2 commitment--CD80, CD86, and IL-12--are not inducible by SR ligation. In addition to macrophages and dendritic cells, B cells also show receptor-mediated uptake and enhanced presentation of maleyl-Ags. Using a monoclonal T cell line to detect peptide-MHC complexes expressed on spleen cells in Ag-injected mice, we find that higher levels of these complexes are generated in vivo from maleyl-proteins and they persist longer than those generated from the native protein. Together, these data suggest that in certain situations, the levels of cognate ligand available and/or the time course of their availability may play a major role in determining the cytokine profiles of the responding T cells in addition to the costimulatory signals implicated so far.
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: N
authors.initials: N
authors.lastname: Singh
authors.forename: S
authors.initials: S
authors.lastname: Bhatia
authors.forename: R
authors.initials: R
authors.lastname: Abraham
authors.forename: S K
authors.initials: SK
authors.lastname: Basu
authors.forename: A
authors.initials: A
authors.lastname: George
authors.forename: V
authors.initials: V
authors.lastname: Bal
authors.forename: S
authors.initials: S
authors.lastname: Rath
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000502:physiology; D006649:Histocompatibility Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D008298:Maleates / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D016207:Cytokines; D006649:Histocompatibility Antigens; D008298:Maleates; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C030272:maleic acid