Decreased signaling competence as a result of receptor overexpression: Overexpression of CD4 reduces its ability to activate p56 super(lck) tyrosine kinase and to regulate T-cell antigen receptor expression in immature CD4 super(+)CD8 super(+) thymocytes

Thymic selection of the developing T-cell repertoire occurs in immature CD4 super(+)CD8 super(+) thymocytes, with the fate of individual thymocytes determined by the specificity of T-cell antigen receptor they express. However, T-cell antigen receptor expression in immature CD4 super(+)CD8 super(+) thymocytes is actively down-regulated in CD4 super(+)CD8 super(+) thymocytes by CD4-mediated tyrosine kinase signals that are generated in the thymus as a result of CD4 engagement by intrathymic ligands. In the present study we have examined the effect of CD4 overexpression in CD4 super(+)CD8 super(+) thymocytes on activation of CD4-associated p56 super(lck) tyrosine kinase and regulation of T-cell antigen receptor expression. This study provides an example in which receptor overexpression leads to decreased receptor signaling competence.