Mechanisms determining cell membrane expression of different γδ TCR chain pairings

Abstract

We investigated the ability of the most common TCR-c and d chains to express on the cell surface. Vc1Cc4 and Vc7Cc1 chains paired with all TCR-d chains tested, whereas Vc4Cc1 chains were found with Vd4 and Vd5, but not with Vd2 or Vd6 chains, and Vc2Cc2 chains were expressed only with Vd5. Mapping studies showed that up to four polymorphic residues influence the different co-expressions of Vc1 and Vc2 chains with Vd chains. Unexpectedly, these residues are not located in the canonical c/d interface, but in the outer part of the cd TCR complex exposed to the solvent. Expression of functional Vd4 or Vd6 chains in Vc2/Vd5 + cells or of functional Vc2Cc2 in Vc1 + cells reduced cell-surface expression of the cd TCR. Taken together, these data show that (i) the Vc/Vd repertoire of mouse cd T cells is reduced by physical constraints in their associations.(ii) Lack of Vc2/Vd expression is due to the formation of aberrant TCR complexes, rather than to an intrinsic inability of the chains to pair and (iii) despite not being expressed at the cell surface, the presence of a functionally rearranged Vc2 chain in cd T cells results in reduced TCR levels. Key words: Chain pairing . gd T cells . Membrane expression . T-cell receptors IntroductionCompared with the ab TCR and most Ig loci, gd TCR have the fewest V genes but are predicted to exert the highest potential for diversity, mostly due to the possible usage of multiple D regions in their TCR-d chains [1]. 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.gd T cells present in distinct anatomical sites show preferential Vg-gene expression [9] and, sometimes, preferential usage of certain combinations of Vg and Vd-gene segments. For example, epidermal gd T-cell in mice express receptors that use Vg5 and Vd1 [10,11], and those present in the epithelia of the female reproductive organs express receptors that use the Vg6 and Vd1 [12]. Their restricted TCR is partly due to the almost exclusive rearrangement of these genes during fetal life [6,7] and, at least for the epidermal cells, due to the selection of cells expressing the right TCR [13]. Another example of restricted Vg/Vd-gene usage concerns a population of gd T cells that share with NK T cells a number of phenotypic and functional characteristics, preferentially localized in the liver and spleen, and expressing receptors that use Vg1 and Vd6.3 [14,15]. Common to all these gd T-cell subsets is not only their restricted usage of Vg and Vd chains, but also their paucity of junctional diversity [11, 12,14] and their fetal or perinatal origin [6][7][8]16].Correspondence: Dr. Pablo Pereira e-mail: pablo.pereira-esteva@pasteur.frwww.e...

The Armadillo (Dasypus novemcinctus): A Witness but Not a Functional Example for the Emergence of the Butyrophilin 3/Vγ9Vδ2 System in Placental Mammals

“…This is an interesting finding, as apparently structural features, which allow pairing of armadillo Vδ2 with Vγ9 are conserved, although no evidence for TRGV9 expression was found. However, pairing of Vδ2 chains is not restricted to Vγ9 TCR chains in humans ( 51 ) even though there are certain pairings of γδ chains in mice that fail to be expressed ( 52 ). PAg-reactivity of human/armadillo heterodimeric γδ TCRs could not be shown.…”

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Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

“…The finding that there are no gd committed DN2 cells in WT mice, in contrast to their Tg counterparts, is not unexpected. The stochastic nature of the rearrangement process, together with the fact that not all combinations of TCRg and TCRd are expressed at the cell surface (11,42), results in many daughter cells being unable to express TCRgd. However, a major implication of this finding is that progenitor cells that fail to express a selectable TCRgd still retain the potential to differentiate into ab-lineage cells.…”

γδ T cell exhaustion: Opportunities for intervention

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