Peptide-MHC stability regulates the efficiency and duration of cross-priming (100.4)

Abstract

Abstract Mechanisms that regulate the recruitment and the accumulation of T cells can impact the magnitude of determinant-specific responses. In this study, we demonstrate that peptide-MHC stability is a regulator of CD8+ T cell cross-priming. We find that increasing the kinetic stability of pMHC for an immunorecessive determinant from SV40 large T antigen, designated site V, overcomes the immunorecessive nature of the determinant. Using an in vivo assay to measure the proportion of naïve T cells that are triggered by cross-priming, we found that enhanced immunogenicity was due to two independent mechanisms regulated by pMHC-stability. 1) Enhanced cross-priming resulted in more efficient recruitment of site V-specific T cells, and 2) extended duration of cross-priming was associated with greater accumulation of site V-specific T cells. Thus, our results suggest that pMHC-stability regulates the magnitude of the CD8+ T cell response by influencing the number of naïve T cells recruited and the extent of T cell expansion. These findings have implications for the design of multivalent CD8+ T cell vaccines targeting subdominant determinants.