Impact of T cell receptor reactivity and HLA phenotype on naive CD8 T cell frequency in humans (160.16)

The impact of major histocompatibility complex (MHC) phenotype on the shaping of the peripheral naive T cell repertoire in humans remains unknown. Here we exploited a pMHC multimer-based sorting approach to analyze the impact of expression of a given human leukocyte Ag (HLA) class I allele on the frequency and quality of peripheral blood and thymic T cells directed against immunodominant self, viral and tumor antigens presented by a human MHC class I allele (HLA-A*02, referred to as A2) in individuals expressing or not this allele. Naive T cell frequencies varied from one antigen specificity to another but were restrained for a given specificity. While A2-restricted T cells showed similar repertoire features and antigenic avidities in A2+ and A2- donors, A2 expression had either a positive, neutral or negative impact on the frequency of A2-restricted naive CD8 T cells, depending on their fine specificity. We also identified in all donors CD4 T cells specific for A2/peptide complexes, whose frequencies were not affected by MHC class I expression, but nevertheless correlated with those of their naive CD8 T cell counterparts. Therefore both selection by self MHC and inherent TCR reactivity regulate the frequency of human naive T cell precursors. Moreover this study also suggests that T cell repertoire shaping by a given self MHC allele is dispensable for generation of immunodominant T cell responses restricted by this particular allele.