Human CD4/CD45RA+ and CD4/CD45RA- T cell subsets express CD4-p56lck complexes, CD4-associated lipid kinases, TCR/CD3-p59fyn complexes, and share similar tyrosine kinase substrates.
T cell activation appears to be regulated by an interplay between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). p56lck and p59fyn have been found to associate with CD4 and TCR-CD3 respectively. The CD45 family of transmembrane PTPases has been shown to be able to regulate the activities of these receptor-associated PTKs in vitro. In man, CD45 contains five different isoforms whose distribution defines subsets of T cells having distinct activation requirements and in vitro functions. Several groups have reported a physical interaction between distinct isoforms of CD45 and CD2, CD4, and the TCR-CD3 complex. Given the potential regulatory interaction between CD45 and PTKs in CD4+ subsets expressing different CD45 isoforms, we have examined CD4 associated and TCR-CD3- associated PTK activities, associated phosphatidyl inositol (PI) kinases and substrates of tyrosine phosphorylation in CD45RA+ and CD45RA- CD4+ T cell lines derived from peripheral blood. Both subsets express CD4-associated p56lck and TCR-CD3-associated p59fyn kinases which exhibit identical in vitro phosphorylation at the Y-394 and Y-420 autophosphorylation sites respectively. Further, both subsets exhibited PI kinases activity associated with CD4-p56lck. Consistent with these observations, anti-CD3 crosslinking induced the phosphorylation of a similar spectrum of intracellular substrates in these CD45RA+ and CD45RA- CD4+ T cell lines. These observations indicate that despite the possible interaction between CD45 isoforms and CD4 or TCR-CD3, the mere expression of the CD45RA isoform does not in and of itself alter the presence of receptor-associated kinases or their intracellular targets.
Rothstein
D M
DM
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
da Silva
A
A
Sugita
K
K
Yamamoto
M
M
Prasad
K V
KV
Morimoto
C
C
Schlossman
S F
SF
Rudd
C E
CE
D019870:1-Phosphatidylinositol 4-Kinase; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D002460:Cell Line; D006801:Humans; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D010770:Phosphotransferases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013379:Substrate Specificity; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens