Developmentally regulated and lineage-specific rearrangement of T cell receptor Vα/δ gene segments

Mechanisms determining cell membrane expression of different γδ TCR chain pairings

“…In this paper we have formally shown that the absence of cells expressing certain Vg/Vd combinations previously observed in adult mice [4,22] results from physical constraints in the association of the chains involved. Thus, not only adult gd TCR are produced from a small number of Vg and Vd-gene segments, but also their V-gene repertoire is further restricted at the level of the combinatorial association of the chains.…”

“…In mice, there are seven Vg genes (referred to as Vg1-Vg7 according to the nomenclature of Heilig and Tonegawa [2]) and about 12 Vd genes [3,4] (see [4] for mouse TCR-d nomenclatures).…”

“…In mice, there are seven Vg genes (referred to as Vg1-Vg7 according to the nomenclature of Heilig and Tonegawa [2]) and about 12 Vd genes [3,4] (see [4] for mouse TCR-d nomenclatures). Of the seven Vg genes, Vg3 is absent or is a pseudogene in most mouse strains [5] and Vg5 and Vg6 rearrange almost exclusively during fetal life [6][7][8], leaving the adult mice with four Vg genes (Vg1, Vg2, Vg4 and Vg7) to constitute the adult repertoire of gd TCR.…”

“…Indeed, transduction of functional Vg2 and Vd6 chains in a CD3 + cell line resulted in the undetectable expression of a gd TCR at the cell surface giving further support to this notion [24]. Similar phenotype analyses performed in humans have revealed that Vd2 (see [9] for the different nomenclatures of TCR-g and TCR-d genes in humans) is rarely, if ever, used in conjunction with Vg segments other than Vg9 and, conversely, that Vd1 is mostly used together with upstream members of the Vg1-gene family [9] and that these preferences cannot be explained by physical constrains in their associations [25].The present study was undertaken to evaluate the mechanisms responsible for the absence of gd T cells bearing defined Vg/Vd combinations observed in normal adult mice [4,22]. By infecting CD3 + cells with retroviral particles containing the most frequently utilized TCR-g and TCR-d chains we have now formally shown that certain Vg/Vd combinations fail to express on the cell surface indicating that physical constrains in their assembly, rather than liganddriven selection, restrict the V-gene usage of adult mouse gd T cells.…”

“…Analyses with available Vg-and Vd-specific mAb have shown the virtual absence of gd T cells co-expressing certain TCR-g and TCR-d chains (i.e. Vg4 and Vd6, Vg2 and Vd4, and Vg2 and Vd6) [4,22] in spite of the fact that these gene segments often rearrange in gd T-cell progenitors, and cells expressing any of these chains represent numerically important populations of thymic and peripheral gd T cells [4,22,23]. The mechanisms responsible for the absence of cells expressing these Vg/Vd combinations have not been directly analyzed, but in experiments analyzing TCR-g and TCR-d rearrangements in adult gd thymocytes, in isotypically included gd T cells, a correlation was found between the presence of functional Vg2 or Vg4 chains not expressed at the cell surface and that of Vd chains that are not found co-expressed with them.…”