Phenotypical trajectories and repertoire architectures in long-lived B and T cell memory

Immunological memory is a key feature of adaptive immunity. Although mechanisms of memory formation have been studied extensively in animal models, we know surprisingly little about the factors influencing memory longevity in humans and the reasons for the strong heterogeneity observed between infections. In my postdoctoral work, I have shown that following an infection that gives rise to long term immunological memory, such as vaccination with attenuated Yellow fever virus (YFV), CD8+ T cell populations specific for different YFV-derived epitopes form two distinct types of memory with different activation patterns, phenotypes and contraction. My hypothesis is that the presence of both types of memory (one more differentiated and the other with more stem-like properties) supports long-term persistence of memory. The goal of the proposed project is: (i) to establish whether memory populations with distinct properties are present among YFV-specific CD4+ T cells and B cells as well, (ii) to examine the interplay between YFV+CD4+ T cells and YFV+B cells and its effects on memory formation and maintenance, and (iii) to ascertain which B cell receptor (BCR) and T cell receptor (TCR) repertoire features (such as clonality and gene segment utilization) associate with each type of memory in YFV+B and T cells. By simultaneously dissecting CD8+, CD4+ and B cell memory to YFV, this study will identify short term correlates of long-term memory and describe TCR/BCR features that favour development of long-lasting memory, ultimately providing important insights for rational vaccine design.