T cell receptor γ cDNA in human fetal liver and thymus: Variable regions of γ chains are restricted to VγI or V9, due to the absence of splicing of the V10 and V11 leader intron

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Abstract
Although complete in‐frame transcripts of the human T cell receptor γ V10 and V11 genes have been described, the corresponding γ chains have never been found in γδ T cell receptors. In this study, we show that the leader intron of all V10 and V11 cDNA isolated from fetal thymus, fetal liver and adult peripheral blood lymphocytes are unspliced. We demonstrate that, due to the absence of splicing, V10 and V11 are pseudogenes and cannot be expressed in γ chains. They are the first pseudogenes of this type described in a rearranging T cell receptor/immunoglobulin locus. Therefore the γ repertoire at the protein level is limited to subgroup VγI and to V9. By analysis of the γ polymerase chain reaction products from total cDNA, we find that the γ locus is active in early ontogeny (8 weeks), as shown by the presence of rearranged V9 and V10 gene transcripts in the liver. At 13 weeks, the VγI genes as well as V9 and V10 have undergone productive rearrangements in the liver, and in the thymus. Most rearrangements, if not all, involve the T cell receptor γ C1 region (JP1, JP, J1 segments) in both tissues, confirming the accessibility of the C1 region in early stages of development.