First Author | Leung BL | Year | 1999 |
Journal | J Immunol | Volume | 163 |
Issue | 3 | Pages | 1334-41 |
PubMed ID | 10415032 | Mgi Jnum | J:119606 |
Mgi Id | MGI:3702835 | Doi | 10.4049/jimmunol.163.3.1334 |
Citation | Leung BL, et al. (1999) TCR alpha beta-independent CD28 signaling and costimulation require non-CD4-associated Lck. J Immunol 163(3):1334-41 |
abstractText | 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. |