The TCR C beta FG loop regulates alpha beta T cell development
Touma, M.; Chang, H-Ching.; Sasada, T.; Handley, M.; Clayton, L.K.; Reinherz, E.L.
Journal of Immunology 176(11): 6812-6823
2006
ISSN/ISBN: 0022-1767 PMID: 16709841 Document Number: 600851
The TCRP chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an alpha beta TCR cavity against which CD3 epsilon gamma may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15 alpha beta TCR transfectants expressing a FG loop-deleted chain (beta Delta FG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type beta-chain (beta wt) upon TCR cross-linking. Furthermore, coimmunoprecipitation studies suggest a weakened association between the CD3 epsilon gamma heterodimer and the beta-chain in TCR complexes containing the beta Delta FG variant. To further investigate the biologic role of the C beta FG loop in development, we competitively reconstituted the thymus of Ly5 congenic or RAG-2(-/-) mice using bone marrow cells from beta wt or beta Delta FG transgenic C57BL/6 (B6) mice. Both beta wt and beta Delta FG precursor cells generate thymocytes representative of all maturational stages. However, beta Delta FG-expressi'ng thymocytes dominate during subsequent development, resulting in an excess of beta Delta FG-expressing peripheral T cells with reduced proliferative and cytokine production abilities upon TCR stimulation. Collectively, our results show that the unique C beta FG loop appendage primarily controls alpha beta T cell development through selection processes.