Engagement of CD4 and CD8 expressed on immature thymocytes induces activation of intracellular tyrosine phosphorylation pathways.
Accumulating data suggest that the target cells for selection events leading to establishment of the mature T cell repertoire are the functionally immature double-positive (CD4+/CD8+) thymocytes, and that the CD4 and CD8 antigens expressed on these cells play important roles in these processes. In an attempt to define the biochemical pathways implicated in these events, we have studied the effects of engagement of accessory molecules on tyrosine protein phosphorylation. The results of our experiments demonstrate that engagement of CD4 and CD8 expressed on double-positive thymocytes is coupled with a rapid tyrosine protein phosphorylation signal. Further analyses have revealed that these two surface molecules are physically associated with the internal membrane tyrosine protein kinase p56lck in immature thymocytes, and that the catalytic function of lck expressed in double-positive thymocytes is significantly enhanced upon engagement of CD4. These data provide evidence that tyrosine-specific protein phosphorylation pathways coupled to the CD4 and CD8 T cell surface antigens are functional in immature thymocytes, and therefore, formally prove that signaling functions of CD4 and CD8 molecules are operative in immature thymocytes.
Veillette
A
A
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Zúñiga-Pflücker
J C
JC
Bolen
J B
JB
Kruisbeek
A M
AM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D016827:CD8 Antigens; D002454:Cell Differentiation; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases