Residual antigen presentation by CD40-licensed DCs instructs memory CD8+ T cells differentiation program to influenza (P1412)

Abstract

Abstract Here we show that residual antigen presentation by CD40-licensed dendritic cells (DCs) tunes memory CD8+ T cell responses to influenza. Primary and secondary CD8+ T cell responses to influenza nucleoprotein (NP) were reduced in Cd40-/- mice. When primed in Cd40-/- mice, NP-specific memory CD8+ T cells responded poorly to re-challenge, even in a CD40 sufficient environment. Defective programming in Cd40-/- mice was due to inefficient late cross-presentation of NP by CD70-expressing CD103-CD11bhi DCs. We demonstrated that residual antigen presentation by CD40 licensed CD70-expressing CD103-CD11bhi DCs prevented apoptosis of IL-2 responding CD8+ T cells and promoted memory CD8+ T cells differentiation by allowing combined TCR- CD25-CD27 signaling during the contraction phase of the primary response. We also show that CD40 signaling preferentially licensed CD70-expressing CD103-CD11bhi DCs to cross-present the more abundant influenza antigens. As a consequence, T cells of different specificities received different memory programing signals during the contraction phase depending on the antigen abundance, and the memory pool result enriched in T cell clones with a TCR repertoire selected for dominant epitopes. Taken together our results suggest that diferential residual antigen presentation by CD40 licensed CD70-expressing CD103-CD11bhi DCs represents a mechanism to enhance the fitness of the memory T cell responses