Characterisation of naïve influenza-specific TCR repertoires in human cord blood (#181)
CD8+ T cell immunity directed at conserved viral epitopes is crucial in providing humans with long-term protection against distinct influenza virus strains. In order to understand how CD8+ T cells successfully confer immune memory, many studies have focused on the prominent M158-66-specific memory T cells population in adult HLA-A*02:01 individuals, generated after repeated exposures to influenza virus. However, it is still not well understood how the pre-existing naïve CD8+ T cell repertoire in humans influences the subsequent response to infection or whether the well characterised dominance of TRBV19 usage in M158-66-specific memory populations is driven by the pre-existing repertoire or selective advantage during the immune response. In our study, we have isolated and characterized naïve A2*M158 specific T cell populations from cord blood samples isolated from multiple HLA-A*02:01 individuals. We have performed paired alpha and beta chain TCR sequence analysis of the naïve populations and further characterized these cells individually by CD27 and CD45RA expression as well as affinity for M158 tetramer, to provide insights into the links between the naïve repertoire and drivers of a successful immune response. Our analysis suggests that a pre-existing TRBV19 bias in cord blood is largely contributing to the dominance seen in adult populations, however, there is still a significant potential for diversity in the TCR repertoire through alpha chain usage.These findings will help to drive design of more appropriate vaccination models whereby knowledge of strengths and weaknesses in pre-existing immune TCR repertoires can be more directly targeted to elicit better outcomes