The major problem in the study of T-cell development is that of tracking thymocytes of a given specificity. Recent studies1-4 have exploited natural correlations between the expression of a particular Vβ gene segment and T-cell receptor (TCR) specificity. We and others (refs 5,6 and M. Davis, personal communication) have taken an alternative approach. We have generated transgenic mice expressing the αβ antigen receptor from the cytotoxic T-lymphocyte clone 2C (ref. 7). In transgenic mice of the same haplotype as the 2C clone, the 2C TCR was expressed on 20-95% of peripheral T cells. Very few of these T cells carried the CD4 antigen; the vast majority were CD4-CD8+ and were able to lyse targets with the same specificity as the original 2C clone. These results indicate that the αβ heterodimer transfers specificity to recipient cells as expected from earlier studies8-11, and that receptor specificity in T-cell repertoire selection is determined by both αβ heterodimer and CD4 or CD8 accessory molecules.
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