Most currently approved vaccines rely on generating a strong antibody response, but few trigger potent memory CD8+ T cells—immune cells that are uniquely equipped to identify and kill pathogen-infected cells and tumor cells. Understanding how to improve the functional characteristics of memory CD8+ T cells could lead to the development of more effective T-cell vaccines and therapeutics.

In a mouse study published online on April 26 in Nature Communications, a team led by Grégoire Lauvau, Ph.D., with lead co-authors Mandy Chin, Ph.D., and Erik Guillen, reports—challenging general dogma about what is needed for an effective memory cell response—that the strength of T-cell receptor (TCR) signaling, and therefore the choice of epitopes (antigen fragments) used in vaccines, is essential for determining how CD8+ T cells integrate chemical signals called cytokines to form robust memory cells that can competitively re-expand upon a secondary antigen encounter. Combining strong TCR and cytokine signals during T-cell priming (vaccination) induces chromatin accessibility in promoters of genes encoding for stem-cell, cell-cycle and calcium-related proteins that correlate with greater T-cell fitness.

Dr. Lauvau is professor of microbiology & immunology at Einstein. Dr. Chin was a postdoctoral fellow at Einstein and is now at EvolveImmune Therapeutics. Mr. Guillen is an M.D./Ph.D. student at Einstein.