The TCR Cβ FG Loop Regulates αβ T Cell Development

Abstract

The TCRβ chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an αβ TCR cavity against which CD3εγ may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15αβ TCR transfectants expressing a FG loop-deleted chain (βΔFG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type β-chain (βwt) upon TCR cross-linking. Furthermore, coimmunoprecipitation studies suggest a weakened association between the CD3εγ heterodimer and the β-chain in TCR complexes containing the βΔFG variant. To further investigate the biologic role of the Cβ FG loop in development, we competitively reconstituted the thymus of Ly5 congenic or RAG-2−/− mice using bone marrow cells from βwt or βΔFG transgenic C57BL/6 (B6) mice. Both βwt and βΔFG precursor cells generate thymocytes representative of all maturational stages. However, βΔFG-expressing thymocytes dominate during subsequent development, resulting in an excess of βΔFG-expressing peripheral T cells with reduced proliferative and cytokine production abilities upon TCR stimulation. Collectively, our results show that the unique Cβ FG loop appendage primarily controls αβ T cell development through selection processes.