The absence of cytotoxic T lymphocyte activity and the failure of MHC class I-restricted T cell receptor (TCR) transgenic thymocytes to mature in CD8α-deficient mice suggest that CD8 may be essential for CD8 lineage commitment. We report that variants of the antigenic peptide that delete TCR transgenic thymocytes from CD8 wild-type but not CD4, up-deficient mice can restore positive selection of CD8 lineage cells in the absence of CD8. The positively selected cells down-regulate CD4, up-regulate TCR, respond to the antigenic peptide, and express CD8β mRNA. Interestingly, there was no enhanced selection of CD4+ T cells, implying that the TCR-MHC interaction, even in the absence of CD8, provided instructive signaling for commitment to the CD8 lineage. Our results are discussed in terms of recent models of T cell lineage commitment.
Bibliographical noteFunding Information:
Correspondence should be addressed to M. J. B. We wish to thank Dr. Stephen Hedrick for helpful discussions and for first separating coreceptor and affinity contributions in a phase diagram. CD8α-deficient mice were the gift of Dr. Tak Mak. Also, we acknowledge the excellent work of D. Wilson for care of the animals, and M. Zollman and B. Dere for technical assistance. This work was supported by the following grants: National Institutes of Health A1–29802, A1–39560, and P32CA09537, and the Howard Hughes Medical Institute.