Antigen-specific murine and human T cells express a polymorphic receptor, consisting of 2 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 2 new chains, termed gamma and delta. These cells express a double negative (CD4-CD8-) phenotype and are predominantly expressed in early T cell population. To achieve a better understanding of the activation requirements and expression of this new receptor at the clonal level, a panel of T cell hybridomas with gamma-delta receptors was established. Analysis of the activation pathways utilized by these cells demonstrated that they are responsive to the same signals (i.e., anti-T3, anti-Thy-1 and con A) as """"""""conventional"""""""" alpha beta T cells. Furthermore, biochemical analysis of T cell hybridomas has demonstrated so far 2 different species of gamma chain and 3 different species of delta chain, thus revealing a diversity in both gamma and delta not expressed at the total population level (i.e., in double negative thymocyte populations from which the hybridomas are derived). Future studies include: (1) 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; (2) development of antigen-specific gamma-delta T cells and hybridomas, such that possible ligands for this new receptor can be identified. The significance of this projects lies in 2 areas: (1) understanding the role of gamma-delta cells in early T cell development, and (2) understanding why this new receptor is engaged in recognition of a wide variety of neoplasms.
