Antigen-specific murine and human T cells express a polymorphic receptor, consisting of two disulfide linked chains, termed alpha and beta, noncovalently linked to a nonpolymorphic complex of proteins, termed T3. The T3 complex plays a vital role in the signal transduction process of T cells. Over the past year, a new type of T cell was discovered, expressing a T3 complex linked to two new chains, termed gamma and delta. These cells express a double negative (CD4-CD8-) phenotype and are predominantly expressed in early T cell populations. To achieve a better understanding of the expression of this new receptor at the clonal level, panels of T-cell hybridomas with gamma delta receptors were established from a variety of sources, i.e., adult thymus, fetal thymus, nude spleen, and nude spleen after thymus transplantation. Biochemical analysis of some of the T-cell hybridomas has demonstrated so far three different species of gamma chain and four different species of delta chain, thus revealing a diversity in both gamma and delta not expressed at the total population level. Furthermore, variable region gene usage for both the delta and the gamma chain appears quite different for gamma delta receptors on cells derived from different sources, and nonrandom pairing of gamma and delta chains was observed. The study is aimed at acquiring a complete picture of the diversity of the expressed gamma delta repertoire, which will involve a combination of biochemical and molecular analysis of the established cell lines. Future studies also include development of monoclonal antibodies specific for gamma and delta chains, such that in vivo and in vitro studies on the effect of such antibodies on gamma delta cells and their role in T-cell development can be explored. The significance of this project lies in the understanding the role of gamma delta cells in early T-cell development.
