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) β chain structure is the large FG loop that protrudes freely into the solvent on the external face of the Cβ domain. We have already shown that a transgene-encoded Vβ8.2⁺ TCR β chain lacking the complete Cβ FG loop supports normal development and function of conventional α/β T cells. Thus, the FG loop is not absolutely necessary for TCR signaling. However, further analysis has revealed that a small population of α/β 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 Vβ8.2⁺ chain lacking the Cβ FG loop cannot pair efficiently with the invariant Vα14-Jα281 TCR α 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 Vα14⁺ TCR α chain is particularly sensitive to TCR-β conformation. Development of NK1.1 T cells appears to need a TCR-β conformation dependent on the presence of the Cβ loop that is not necessarily required for assembly and function of TCRs on most α/β T cells.