Cutting Edge: An mRNA Platform to Create Isolated, Monospecific Th1 Responses

Helper T cells (T _CD4 ) are lynchpins of adaptive immune responses. Since each T _CD4 expresses a single T cell receptor, recognizing an epitope within major histocompatibility complex class II (MHCII), it is often desirable to study a population that responds to the same epitope. We devised a novel method of selective immunization to produce a robust, monospecific T _CD4 in mice using a modular mRNA vector. The vector encodes the target epitope attached via flexible linker to MHCII. Immunization with this mRNA selectively elicits T _CD4 responses across a range of epitopes and MHCII alleles. These T _CD4 show robust, polyfunctional Th1 cytokine release when evaluated in vitro . Additionally, we tested the activity of these T _CD4 cells during Salmonella enterica infection, a model of Th1-dependent immune response, and demonstrated their efficacy in vivo in curtailing infection.