Impaired NK1.1 T cell development in mice transgenic for a T cell receptor β chain lacking the large, solvent-exposed Cβ FG loop

A striking feature of the T cell receptor (TCR) beta chain structure is the: large FG loop that protrudes freely into the solvent on the external face of the C beta domain. We have already shown that a transgene-encoded V beta 8.2(+) TCR beta chain lacking the complete C beta FG loop supports normal development and function of conventional alpha/beta T cells. Thus, the FG loop is not absolutely necessary for TCR signaling. However, further analysis has revealed that a small population of alpha/beta T cells coexpressing NK1.1 are severely depleted in these transgenic mice. The few remaining NK1.1 T cells have a normal phenotype but express very low levels of TCR. We find that the TCR V beta 8.2(+) chain lacking the C beta FG loop cannot pair efficiently with the invariant Va14-Jol281 TCR alpha chain commonly expressed by this T cell family. Consequently, fewer NK1.1 T cells develop in these mice. Our results suggest that expression of the V alpha 14(+) TCR alpha chain is particularly sensitive to TCR-beta conformation. Development of NK1.1 T cells appears to need a TCR-beta conformation dependent on the presence of the C beta loop that is not necessarily required for assembly and function of TCRs on most alpha/beta T cells.