Human γδ TCR Repertoires in Health and Disease

The T cell receptor (TCR) repertoires of γδ T cells are very different to those of αβ T cells. While the theoretical TCR repertoire diversity of γδ T cells is estimated to exceed the diversity of αβ T cells by far, γδ T cells are still understood as more invariant T cells that only use a limited set of γδ TCRs. Most of our current knowledge of human γδ T cell receptor diversity builds on specific monoclonal antibodies that discriminate between the two major subsets, namely Vδ2⁺ and Vδ1⁺ T cells. Of those two subsets, Vδ2⁺ T cells seem to better fit into a role of innate T cells with semi-invariant TCR usage, as compared to an adaptive-like biology of some Vδ1⁺ subsets. Yet, this distinction into innate-like Vδ2⁺ and adaptive-like Vδ1⁺ γδ T cells does not quite recapitulate the full diversity of γδ T cell subsets, ligands and interaction modes. Here, we review how the recent introduction of high-throughput TCR repertoire sequencing has boosted our knowledge of γδ T cell repertoire diversity beyond Vδ2⁺ and Vδ1⁺ T cells. We discuss the current understanding of clonal composition and the dynamics of human γδ TCR repertoires in health and disease.