Significance of adhesion molecules in differentiation and activation of thymocytes.

In the sequential steps in the T lymphocyte differentiation, the traffic of T cell progenitors through thymic tissue and contact with the thymic stromal cells have been considered to be most crucial, and stromal cells have been regarded as the most effective partner of this contact. Extracellular matrix, such as fibronectin (FN), are ubiquitously distributed within the body and considered to be involved in the first step of cell adhesion. For the lymphoid cells which do not have strong contacts with adjacent cells, the adhesion to thymic stromal cells or extracellular matrix must be very important for the initial differentiational process occurred in thymic microenvironments. To elucidate the function of adhesion molecules on T cell development and activation, we have generated monoclonal antibodies, 7D3 and 8H3, which respectively inhibit thymocyte adhesion either to thymic epithelial cells or fibronectin. Furthermore, 8H3 antibody stimulate thymocyte proliferation. Since both antigens were already expressed on immature thymocytes which do not yet express T cell receptor complex, such antigen-independent interactions may play crucial roles in early T cell development. Based on partial amino acids sequences of affinity-purified 8H3 polypeptides, putative cDNA clones encoding 8H3 molecules were isolated and further study to identify primary structure of the cDNA clones are in progress.