The allorestricted cytotoxic T-cell concept.

Hematopoietic cells from an HLA-A0201⁺ patient present a hematopoietic epitope (eg, a CD45-derived peptide), represented by the yellow tick, on surface HLA-A0201 molecules. Because of tolerance, T cells recognizing this self-peptide have been clonally deleted in the patient. In contrast, in an HLA-A0201⁻donor who shares this antigen, the epitope cannot be presented because of the lack of HLA-A0201 on the cells; consequently T cells directed against this epitope are not deleted. Stimulation of such T cells with HLA-A0201⁺ APCs pulsed with the epitope may generate allorestricted CTLs that recognize leukemic and normal host hematopoietic cells, which coexpress HLA-A0201 and the hematopoietic antigen, but that do not recognize host nonhematopoietic tissues, which do not express the antigen or donor hematopoietic cells from the graft and are HLA-A0201⁻.