Class I MHC molecules on hematopoietic cells can support intrathymic positive selection of T cell receptor transgenic T cells

The identity of cells that mediate positive selection of CD8(+) T cells was investigated in two T cell receptor (TCR) transgenic systems. Irradiated b eta(2)-micro-globulin mutant mice or mice with mutations in both the K-b an d D-b genes were repopulated with fetal liver cells from class I+ TCR trans genic mice, In the case of the 2C TCR, mature transgene-expressing CD8(+) T cells appeared in the thymuses of the chimeras and in larger numbers in th e peripheral lymphoid organs. These CD8(+) T cells were functional, exhibit ed a naive, resting phenotype, and were mostly thymus-dependent. Their deve lopment depended on donor cell class I expression. These results establish that thymic hematopoietic cells can direct positive selection of CD8(+) T c ells expressing a conventional TCR, In contrast, no significant development of HY (male antigen)-TCR+ CD8(+) T cells was observed in class I+ into cla ss I-deficient chimeras. These data suggest that successful positive select ion directed by hematopoietic cells depends on specific properties of the T CR or its thymic ligands, The possibility that hematopoietic cell-induced, positive selection occurs only with TCRs that exhibit relatively high avidi ty interactions with selecting ligands in the thymus is discussed.