T-LYMPHOCYTES FROM HUMAN CHIMERAS DO RECOGNIZE ANTIGEN IN THE CONTEXTOF ALLOGENEIC DETERMINANTS OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

Human stem cells from the fetal liver can be transplanted to immunodef icient patients and reconstitute their immunity by giving rise to immu nocompetent T lymphocytes of donor origin. Despite full HLA mismatch b etween donor and host, the helper T cells and the cytotoxic T cells wh ich develop in these chimeric patients are totally functional. They re cognize the antigenic peptides presented in the context of the foreign HLA molecules of the recipient, indicating that donor stem cells have been positively selected in the host environment, probably the thymic epithelial cells. By contrast, negative selection appears to be impos ed upon T cells by donor hemopoietic cells, probably macrophages or de ndritic cells, migrating from the transplant to the host thymus. Clona l deletion is then responsible for tolerance to donor HLA antigens, wh ile clonal anergy explains tolerance to host HLA antigens.