Two properties of T lymphocytes are the ability to respond to foreign antigens in association with molecules of the self major histocompatibility complex (MHC) and the unresponsiveness towards self MHC molecules alone. Important progress has been made in understanding the process by which T lymphocytes recognize antigen through the cloning and characterization of the alpha and beta genes of the T cell receptor for antigen (TCR). Despite this progress, the precise mechanisms of thymic education, in particular the self-tolerance education, remain poorly understood. Beside the alpha/beta TCR for antigen, a second TCR called gamma/delta has been described at the protein level. The gamma/delta TCR has frequently been found in immature T cells and thymocytes and is therefore thought to play a role during the early events of thymic T cell development. This project aims to attempt to clone the human delta chain gene as well as to study its relationship with the other TCR genes, in particular the alpha gene. In the course of characterizing immature human T cell tumors, we detected a novel 2 kb alpha-related transcript. cDNA clones corresponding to this transcript established that a new genetic element (T early alpha = TEA), had been spliced to the alpha constant region. The expression of TEA is highest in early fetal thymus and declines during T cell maturation. TEA is present in the germ-line configuration in gamma/delta expressing cells and is deleted in mature alpha/beta expressing cells. Surprisingly the TEA probe detected a limited number of rearranged band in a non-clonal thymic DNA. We are currently characterizing these rearrangements, and their relationship to immature and mature TCR gene expression.
