dc.contributor.author | Sasada, Tetsuro | |
dc.contributor.author | Touma, Maki | |
dc.contributor.author | Chang, Hsiu-Ching | |
dc.contributor.author | Clayton, Linda K. | |
dc.contributor.author | Wang, Jia-huai | |
dc.contributor.author | Reinherz, Ellis L. | |
dc.date.accessioned | 2019-10-17T05:18:55Z | |
dc.date.issued | 2002 | |
dc.identifier.citation | Sasada, Tetsuro, Maki Touma, Hsiu-Ching Chang, Linda K. Clayton, Jia-huai Wang, and Ellis L. Reinherz. 2002. “Involvement of the TCR Cβ FG Loop in Thymic Selection and T Cell Function.” The Journal of Experimental Medicine 195 (11). Rockefeller University Press: 1419–31. doi:10.1084/jem.20020119. | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.issn | 1540-9538 | |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41555755 | * |
dc.description.abstract | The asymmetric disposition of T cell receptor (TCR) Cbeta and Calpha ectodomains creates a cavity with a side-wall formed by the rigid Cbeta FG loop. To investigate the significance of this conserved structure, we generated loop deletion (betaDeltaFG) and betawt transgenic (tg) mice using the TCR P subunit of the N15 CTL. N15betawt and N15betaDeltaFG H-2(b) animals have comparable numbers of thymocytes in S phase and manifest developmental progression through the CD4(-)CD8(-) double-negative (DN) compartment. N15betaDeltaFG facilitates transition from DN to CD4(+)8(+) double-positive (DP) thymocytes in recombinase activating gene (RAG)-2(-/-) mice, showing that pre-TCR function remains. N15betaDeltaFG animals possess similar totwofold more CD8(+) single-positive (SP) thymocytes and lymph node T cells, consistent with enhanced positive selection. As an altered Vet repertoire observed in N15betaDeltaFG mice may confound the deletion's effect, we crossed N15alphabeta TCR tg RAG-2(-/-) with N15betaDeltaFG tg RAG-2(-/-) H-2(b) mice to generate N15alphabeta RAG-2(-/-) and N15alphabeta.betaDeltaFG RAG-2(-/-) littermates. N15alphabeta.betaDeltaFG RAG-2(-/-) mice show an 8-10-fold increase in DP thymocytes due to reduced negative selection, as evidenced by diminished constitutive and cognate peptide-induced apoptosis. Compared with N15alphabeta, N15alphabeta.betaDeltaFG T cells respond poorly to cognate antigens and weak agonists. Thus, the Cbeta FG loop facilitates negative selection of thymocytes and activation of T cells. | |
dc.language.iso | en_US | |
dc.publisher | Rockefeller University Press | |
dash.license | LAA | |
dc.title | Involvement of the TCR Cβ FG Loop in Thymic Selection and T Cell Function | |
dc.type | Journal Article | |
dc.description.version | Version of Record | |
dc.relation.journal | The Journal of Experimental Medicine | |
dash.depositing.author | Wang, Jia-Huai::0ea01606c2ad0a55493be0a19705594c::600 | |
dc.date.available | 2019-10-17T05:18:55Z | |
dash.workflow.comments | 1Science Serial ID 110082 | |
dc.identifier.doi | 10.1084/jem.20020119 | |
dash.source.volume | 195;11 | |