The ability to generate cytotoxic T lymphocyte responses to minor H antigens offers a potent tool for the study of self-tolerance and self-recognition. Results obtained in this system have thus far demonstrated 1) that the self + X T cell repetoire is highly cross-reactive for allogeneic MHC determinents suggesting that the response to allogenic MHC antigens is comprised of multiple self + X specificities and 2) that self minor H determinents tolerize T cells only in association with self MHC determinents so that tolenance induction to non MHC self components is restricted by MHC encoded products. We are currently examining the role of antigen processing in the generation of the cytotoxic response to minor-H antigens. Results so far indicate that 1) Macrophages are requisite for minor H specific CTL generation in vitro. 2) The minor antigens need not be synthesized by the antigen presenting cell but can be acquired in vitro by macrophages and subsequently presented in an immunogenic fashion. 3) The generation of the CTL by non antigen bearing APC's is inhibitable by antibodies to the T4 molecule expressed by Ia-restricted T helper cells.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005107-05
Application #
3962954
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code