Evolution and function of the TCR Vgamma9 chain repertoire: It’s good to be public

Abstract

Lymphocytes expressing a T cell receptor (TCR) composed of Vgamma9 and Vdelta2 chains represent a minor fraction of human thymocytes. Extrathymic selection throughout post-natal life causes the proportion of cells with a Vgamma9-JP rearrangement to increase and elevates the capacity for responding to non-peptidic phosphoantigens. Extrathymic selection is so powerful that phosphoantigen-reactive cells comprise about 1 in 40 circulating memory T cells from healthy adults and the subset can be expanded rapidly upon infection or in response to malignancy. Skewing of the gamma delta TCR repertoire is accompanied by selection for public gamma chain sequences such that many unrelated individuals overlap extensive in their circulating repertoire. This type of selection implies the presence of a monomorphic antigen-presenting molecule that is an object of current research but remains incompletely defined. While selection on a monomorphic presenting molecule may seem unusual, similar mechanisms shape the alpha beta T cell repertoire including the extreme examples of NKT or mucosal-associated invariant T cells (MAIT) and the less dramatic amplification of public Vbeta chain rearrangements driven by individual MHC molecules and associated with resistance to viral pathogens. Selecting and amplifying public T cell receptors whether alpha beta or gamma delta, are important steps in developing an anticipatory TCR repertoire. Cell clones expressing public TCR can accelerate the kinetics of response to pathogens and impact host survival.

Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution

“…There is no information about its influence on graft gd T cell distribution. In this article, we show that donor CMV positivity is associated with a high clonality, increased frequency of hyperexpanded clones, and a reduced usage of the V9-JP pair, the most abundant rearrangement present in peripheral blood (15,43). These changes are probably due to adaptive clonal expansion of distinct TRG clones in response to CMV (15).…”

Human γδ T‐cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

“…Analyses of the CDR3d region showed the conserved hydrophobic amino acid at position 97 ( Supplementary table 5), as in phosphoantigenreactive TCRs (L, V, I, A and M). 24 We speculate that in our system, IAV infection may upregulate phosphoantigen metabolites, given the similarities of the CDR3 region with phosphoantigen-reactive cd TCRs.…”

Human γδ TCR Repertoires in Health and Disease

“…This leads to a differential nucleotype usage of fetal and adult germline Vγ9JP clones [28,33,63]. Its CDR3 region seems to be prototypic for pAg recognition by Vγ9Vδ2 + T cells, and is a major contributor to the length homogenization to around 14 amino acids observed in the Vγ9 chain repertoire [62,64,65]. We might speculate that this simple rearrangement, and thus the length homogenization, coevolved with the pAg sensing ability of Vγ9Vδ2 + TCRs and the conserved binding of Vγ9 to BTN2A1 [18,21].…”