Epitope density influences CD8+ memory T cell differentiation.
BACKGROUND
The generation of long-lived memory T cells is critical for successful vaccination but the factors controlling their differentiation are still poorly defined. We tested the hypothesis that the strength of T cell receptor (TCR) signaling contributed to memory CD8(+) T cell generation.


RESULTS
We manipulated the density of antigenic epitope presented by dendritic cells to mouse naïve CD8(+) T cells, without varying TCR affinity. Our results show that a two-fold decrease in antigen dose selectively affects memory CD8(+) T cell generation without influencing T cell expansion and acquisition of effector functions. Moreover, we show that low antigen dose alters the duration of the interaction between T cells and dendritic cells and finely tunes the expression level of the transcription factors Eomes and Bcl6. Furthermore, we demonstrate that priming with higher epitope density results in a 2-fold decrease in the expression of Neuron-derived orphan nuclear receptor 1 (Nor-1) and this correlates with a lower level of conversion of Bcl-2 into a pro-apoptotic molecule and an increased number of memory T cells.


CONCLUSIONS
Our results show that the amount of antigen encountered by naïve CD8(+) T cells following immunization with dendritic cells does not influence the generation of functional effector CD8(+) T cells but rather the number of CD8(+) memory T cells that persist in the host. Our data support a model where antigenic epitope density sensed by CD8(+) T cells at priming influences memory generation by modulating Bcl6, Eomes and Nor-1 expression.
Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montreal, Quebec, Canada.
Julie
J
Leignadier
Nathalie
N
Labrecque
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory
D000939:Epitopes