T-CELL RECEPTOR-GAMMA CDNA IN HUMAN FETAL LIVER AND THYMUS - VARIABLE REGIONS OF GAMMA-CHAINS ARE RESTRICTED TO V-GAMMA-I OR V9, DUE TO THE ABSENCE OF SPLICING OF THE V10 AND V11 LEADER INTRON

Although complete in-frame transcripts of the human T cell receptor gamma V10 and V11 genes have been described, the corresponding gamma chains have never been found in gamma delta 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 gamma chains. They are the first pseudogenes of this type described in a rearranging T cell receptor/immunoglobulin locus. Therefore the gamma repertoire at the protein level is limited to subgroup V gamma I and to V9. By analysis of the gamma polymerase chain reaction products from total cDNA, we find that the gamma 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 V gamma I 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 gamma C1 region (JP1, JP, J1 segments) in both tissues, confirming the accessibility of the C1 region in early stages of development.