Activated CD4+ T helper cells release TCR-enriched nanoscale membrane vesicles (ectosomes) that are transferred to antigen-primed B cells, where ectosomal TCRs engage and cluster cognate pMHCII complexes to trigger intracellular signaling and class-switched antibody production, constituting a quantitatively substantial mode of T cell help that accounts for approximately 50% of antibody responses and can be synthetically reconstituted to boost immune responses in aged mice.

Protective antibody-mediated immunity requires effective T cell-mediated help. Recognition of peptide antigens presented by major histocompatibility complex class II molecules (pMHCII), via cognate T cell antigen receptors (TCR), activates CD4+ T helper cells to upregulate expression of CD40L and helper cytokines. CD40L-CD40 interactions at T-B cell synapses and secreted cytokines are well established mediators of T cell help. Whether engaged pMHCII also transmits signals that help B cells remains unresolved. Here, we show that TCR-enriched nanoscale vesicles shed by activated T cells (ectosomes) are transferred to antigen-primed B cells, where they engage and cluster cognate pMHCII, triggering signaling and specific IgG antibody production. Disruption of ectosome release attenuates B cell antibody production, while native and synthetic ectosomes boost antibody responses. We conclude that T cell ectosomes constitute a new modality of help for B cells, delivered through engagement of pMHCII by cognate ectosomal TCR.