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Updated: Aug 13, 2026

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
Published on: October 25, 2016
TCR alpha beta-independent CD28 signaling and costimulation require non-CD4-associated Lck
B L Leung1, L Haughn, A Veillette
1Department of Immunology, University of Toronto, Arthritis and Immune Disorder Research Centre, Ontario, Canada.
Abstract:
Whether the sequelae of signals generated through CD28 either directly or in circumstances of costimulation require proximal events mediated by p56lck remains contentious. We demonstrate that CD4-, but not CD4+ clonal variants respond to CD28-specific mAb with both early and late indicators of activation. Forced expression of A418/A420-mutated CD4 or wild-type CD4 in the CD4- variant recapitulated the CD28-mediated responses of the CD4- and CD4+ variants, respectively. The implicated involvement of non-CD4-associated Lck is formally demonstrated by overexpressing S20/S23 Lck or wild-type Lck in CD4+ variants. The former, but not latter, rescues direct CD28 signaling, and supports costimulation. The results demonstrate that constitutive levels of non-CD4-associated Lck functionally limit CD28-mediated signaling.
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