We use chimeric antibodies to deliver antigens to specific DC subsets in vivo. By targeting self antigen to DEC-205+ DCs (cDC1), we have shown that in autoimmune NOD mice, CD8 DCs are not able to induce CD4+ T cell tolerance and instead induce expansion and IFN gamma production. CD40/CD40L interactions are one pathway that is important in this setting: when a blocking antibody specific for anti-CD40L was given with anti-DEC-205 antigen, T cell responses were more tolerogenic. CD11b+ cDC2 dendritic cells express DCIR2 on their surface, and antibodies specific for DCIR2 can be used to target antigens to this DC subset. In contrast to the responses elicited by DEC205+ DCs, DCIR2+ DCs are able to induce a more tolerogenic response in self-specific T cells, characterized by less expansion, increased apoptosis and less IFN-gamma even in this chronic autoimmune context. In addition, anti-DCIR2-targeted BDC peptide inhibits diabetes development. By comparing gene expression in beta cell-specific T cells early after in vivo stimulation with either DEC205+ or DCIR2+ DCs, we have identified genes that are expressed at higher levels in T cells stimulated with the more tolerogenic DCIR2+ DCs. One of these tolerance-associated genes is the transcriptional regulator zbtb32. Overexpression of zbtb32 in T cells elicits a response similar to DCIR2 DC stimulation, with decreased expansion, IFN gamma production and inhibition of diabetes development. These results are now online in a publication in the journal Diabetes.