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 beta(2)-microglobulin mutant mice or mice with mutations in both the K(b) and D(b) genes were repopulated with fetal liver cells from class I(+) TCR transgenic 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 the peripheral lymphoid organs. These CD8(+) T cells were functional, exhibited a naive, resting phenotype, and were mostly thymus-dependent. Their development depended on donor cell class I expression. These results establish that thymic hematopoietic cells can direct positive selection of CD8(+) T cells expressing a conventional TCR. In contrast, no significant development of HY (male antigen)-TCR(+) CD8(+) T cells was observed in class I(+) into class I-deficient chimeras. These data suggest that successful positive selection directed by hematopoietic cells depends on specific properties of the TCR or its thymic ligands. The possibility that hematopoietic cell-induced, positive selection occurs only with TCRs that exhibit relatively high avidity interactions with selecting ligands in the thymus is discussed.
Zerrahn
J
J
Department of Molecular Biology, Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Volkmann
A
A
Coles
M C
MC
Held
W
W
Lemonnier
F A
FA
Raulet
D H
DH
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002678:Chimera; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell