MODULATION OF T-CELL CYTOKINE PROFILES AND PEPTIDE-MHC COMPLEX AVAILABILITY IN-VIVO BY DELIVERY TO SCAVENGER RECEPTORS VIA ANTIGEN MALEYLATION

We have previously shown that conversion of proteins to scavenger rece ptor (SR) ligands by maleylation increases their immunogenicity, We no w show that maleyl-Ag-immune spleen cells make relatively more IFN-gam ma and less IL-4 or IL-10 than native Ag-immune cells, This is also re flected in the IgG1:IgG2a ratios in Abs generated in vivo. SR engageme nt on macrophages does not alter their surface levels of the adhesive/ costimulatory molecules CD11a/CD18, CD11b/CD18, CD24, CD54, or CD40, n or does it enhance their ability to support anti-CD3-driven proliferat ion of naive T cells in vitro. Costimulatory molecules implicated in d ifferential Th1/Th2 commitment-CD80, CD86, and IL-12-are not inducible by SR ligation. In addition to macrophages and dendritic cells, B cel ls also show receptor-mediated uptake and enhanced presentation of mal eyl-Ags, Using a monoclonal T cell line to detect peptide-MHC complexe s expressed on spleen cells in Ag-injected mice, we find that higher l evels of these complexes are generated ill vivo from maleyl-proteins a nd they persist longer than those generated from the native protein. T ogether, 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 resp onding T cells in addition to the costimulatory signals implicated so far.