TCR alpha beta-independent CD28 signaling and costimulation require non-CD4-associated Lck
Leung, B.L.; Haughn, L.; Veillette, A.; Hawley, R.G.; Rottapel, R.; Julius, M.
Journal of Immunology 163(3): 1334-1341
1999
ISSN/ISBN: 0022-1767 PMID: 10415032 Document Number: 508958
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.