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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies, Monoclonal / pharmacology
-
CD28 Antigens / genetics
-
CD28 Antigens / immunology
-
CD28 Antigens / physiology*
-
CD4 Antigens / biosynthesis
-
CD4 Antigens / genetics
-
CD4 Antigens / physiology*
-
Cell Division / immunology
-
Cell Line
-
Clone Cells
-
Cysteine / genetics
-
Genetic Vectors
-
Lymphocyte Activation / immunology*
-
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / biosynthesis
-
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
-
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Mutant Strains
-
Receptors, Antigen, T-Cell, alpha-beta / immunology
-
Receptors, Antigen, T-Cell, alpha-beta / physiology*
-
Retroviridae / genetics
-
Retroviridae / immunology
-
Signal Transduction / immunology*
-
T-Lymphocyte Subsets / cytology
-
T-Lymphocyte Subsets / enzymology
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / metabolism
Substances
-
Antibodies, Monoclonal
-
CD28 Antigens
-
CD4 Antigens
-
Receptors, Antigen, T-Cell, alpha-beta
-
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
-
Cysteine