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The Journal of Immunology, 2001, 167: 4311-4320.
Copyright © 2001 by The American Association of Immunologists

CD4 Promotes Breadth in the TCR Repertoire1

Qi Wang*, Laurent Malherbe{dagger}, DongJi Zhang*, Kurt Zingler*, Nicolas Glaichenhaus{dagger} and Nigel Killeen2,*

* Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; and {dagger} Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6097, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France

A diverse population of MHC class II-restricted CD4 lineage T cells develops in mice that lack expression of the CD4 molecule. In this study, we show that the TCR repertoire selected in the absence of CD4 is distinct, but still overlapping in its properties with that selected in the presence of CD4. Immunization of mice lacking CD4 caused the clonal expansion of T cells that showed less breadth in the range of Ag-binding properties exhibited by their TCRs. Specifically, the CD4-deficient Ag-specific TCR repertoire was depleted of TCRs that demonstrated low-affinity binding to their ligands. The data thus suggest a key role for CD4 in broadening the TCR repertoire by potentiating productive TCR signaling and clonal expansion in response to the engagement of low-affinity antigenic ligands.




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