The recognition structures of T cells have been examined using anti-receptor antibodies and anti-T cell surface antigen specific antibodies prepared against cytotoxic T cell clones. Monoclonal antibodies produced from mice and hamsters immunized against the CTL clones have been identified which react with the T cell receptor and other cell surface antigens. One mAb has been generated that specifically activates CTL clones by binding in a clonotypic fashion to the T cell receptor. This mAb, 83-7-2, precipitates a 90 kd heterodimeric glycoprotein similar to that observed for other anti-receptor antibodies. The activation of CTL by the mAb resulted in lysis of Fc-receptor targets that did not express the nominal alloantigen recognized by the clone. In addition, a series of other monoclonal antibodies which recognize an Ly6-linked molecule on the surface o the cytotoxic T cell clones has been generated. These monoclonal antibodies appear to subdivide class I specific CTL into two distinct populations and one such mAb, 143-4-2 can activate CTL clones and a subset of Lyt2+ T cells. Further studies will be designed to analyze the monoclonal antibodies which have been developed and to better define the structural determinants expressed on cytotoxic T cells which are involved in T cell activation. Most recently, a mAb reacting with the murine equivalent of the T cell receptor associated T3-epsilon protein has been developed. This monoclonal antibody immunoprecipates the whole T cell receptor complex under mild denaturing conditions. It has been used to identify a novel T cell receptor on the surface of fetal thymocytes, peripheral T cells, and adult thymocytes. This T cell receptor complex includes a newly identified T cell receptor gene, the gamma, delta receptor. Current studies are underway to examine the role of T cells expressing the gamma, delta in T cell development and tolerence induction.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005112-06
Application #
3939245
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code