TCR-enriched microvesicles provide antigen-specific help for class-switched antibody production

Abstract

Abstract Extracellular vesicles have shown essential roles in various biological processes, mainly through mediating cell-cell communications by its surface and internal cargo. Recently it was found that activated T cells release TCR enriched microvesicles (Tc-MV) from immunological synapse, but the function of Tc-MV is still a mystery. By analyzing proteomics and miRNA profiles of Tc-MV derived from mouse OT-II CD4 T cells (OVA323–339 specific), we found Tc-MV are enriched with proteins related to T cell helper function, including TCRs, CD40L, CD28, ICOS, OX40 and LFA-1, and also contained B cell function involved miRNAs, such as miR-21a-5p, miR-28a-3p, miR-155-5p and miR-210-3p. Accordantly, by in vitro coculture, OT-II Tc-MV could promote NP-specific B cells to secret IgG when cognate antigen NP-OVA was present, similarly Tc-MV from SMARTA T cell (LCMV GP61–80 specific) could promote B cells with antigen NP-GFP-GP61–80, but switching either the MV or the antigens in these two systems dampened the antibody production, suggesting Tc-MV help B cells in an antigen specific manner. The helper function of the Tc-MV was also confirmed in vivo by serum antibody production of Rag1−/− mice transferred with Tc-MV and B cells and followed by immunization, importantly the endogenous Tc-MV were found in the serum of the WT mice post-immunization, demonstrating a fundamental role of Tc-MV in the physiological condition. In conclusion, our findings revealed a critical role of Tc-MV in promoting antigen specific antibody production of B cells, which can be exploited for vaccine design. Supported by University of Michigan Startup Funds and NIH: R01AI134999.