Further evidence for a sequentially ordered activation of T cell rearranging gamma genes during T lymphocyte differentiation.

Recently, we have shown that the majority of human peripheral lymphocytes with a T cell receptor (TcR) gamma/delta receptor use a unique gamma chain recognized by the anti-TigammaA monoclonal antibody. This predominantly expressed gamma protein is encoded by a rearranged gene where the V9 segment has joined the JP segment located upstream of the C gamma 1 region (TRGC1). Peripheral TigammaA+ cells were further studied here to shed light on the relation between the two types of TRG rearrangements namely those involving the first (TRG1) vs. the second (TRG2) J-C region. Thirteen clones reactive with anti-TigammaA were tested; it was found that the second TRG allele (i.e., the one which does not involve V9-JP) of these cells was either in germ-line configuration or, more frequently, rearranged with a downstream V gamma gene joined to a J segment of the TRG1 region. These data suggest that productive rearrangements on TRG1 leading to the production of a surface-expressed gamma chain occur before rearrangements involving the TRG2 region. It supports the view that TRG genes are subjected to a sequentially ordered activation during the process of T lymphocyte differentiation.