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. Antisera produced in mice, rats, and hamsters against the CTL clones show specific reactivity and immunoprecipitation of receptor molecules on the cytotoxic T cells as well as other molecules which appear to be critical to T cell recognition. Present studies are designed to look at monoclonal antibodies prepared against 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 of 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. Current studies are underway to develop monoclonal antibodies against isotypic determinations on the variable regions of the T cell receptor. In addition, 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.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005112-04
Application #
3962958
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code