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The TCR C FG Loop Regulates T Cell Development¹

Maki Touma^*, Hsiu-Ching Chang^*,, Tetsuro Sasada^*,, Maris Handley^*, Linda K. Clayton^*, and Ellis L. Reinherz^2,*,

^* Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; and Department of Medicine, Harvard Medical School, Boston, MA 02115

The TCR chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an TCR cavity against which CD3 may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15 TCR transfectants expressing a FG loop-deleted chain (FG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type -chain (wt) upon TCR cross-linking. Furthermore, coimmunoprecipitation studies suggest a weakened association between the CD3 heterodimer and the -chain in TCR complexes containing the FG variant. To further investigate the biologic role of the C FG loop in development, we competitively reconstituted the thymus of Ly5 congenic or RAG-2^–/– mice using bone marrow cells from wt or FG transgenic C57BL/6 (B6) mice. Both wt and FG precursor cells generate thymocytes representative of all maturational stages. However, FG-expressing thymocytes dominate during subsequent development, resulting in an excess of FG-expressing peripheral T cells with reduced proliferative and cytokine production abilities upon TCR stimulation. Collectively, our results show that the unique C FG loop appendage primarily controls T cell development through selection processes.

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