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Publication : The TCR C beta FG loop regulates alpha beta T cell development.

First Author  Touma M Year  2006
Journal  J Immunol Volume  176
Issue  11 Pages  6812-23
PubMed ID  16709841 Mgi Jnum  J:131794
Mgi Id  MGI:3774478 Doi  10.4049/jimmunol.176.11.6812
Citation  Touma M, et al. (2006) The TCR C beta FG loop regulates alpha beta T cell development. J Immunol 176(11):6812-23
abstractText  The TCRbeta chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an alphabeta TCR cavity against which CD3epsilongamma may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15alphabeta TCR transfectants expressing a FG loop-deleted chain (betaDeltaFG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type beta-chain (betawt) upon TCR cross-linking. Furthermore, coimmunoprecipitation studies suggest a weakened association between the CD3epsilongamma heterodimer and the beta-chain in TCR complexes containing the betaDeltaFG variant. To further investigate the biologic role of the Cbeta FG loop in development, we competitively reconstituted the thymus of Ly5 congenic or RAG-2-/- mice using bone marrow cells from betawt or betaDeltaFG transgenic C57BL/6 (B6) mice. Both betawt and betaDeltaFG precursor cells generate thymocytes representative of all maturational stages. However, betaDeltaFG-expressing thymocytes dominate during subsequent development, resulting in an excess of betaDeltaFG-expressing peripheral T cells with reduced proliferative and cytokine production abilities upon TCR stimulation. Collectively, our results show that the unique Cbeta FG loop appendage primarily controls alphabeta T cell development through selection processes.
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