Molecular analysis of the interaction of p56lck with the CD4 and CD8 antigens.
The CD4 and CD8 antigens on the surface of T cells appear to bind to major histocompatibility complex (MHC) class II and I antigens, respectively. These antigens also synergize with the Ti(TcR)/CD3 complex in the potentiation of T-cell proliferation. Our earlier work demonstrated that the CD4 and CD8 receptors are coupled to a protein-tyrosine kinase termed p56lck from normal and transformed T lymphocytes. The p56lck protein is a member of the src family and its homology with receptor-kinases such as the epidermal growth factor receptor (EGFR) make it an important candidate in signal transduction. In this paper, we show in transfectants that p56lck interacts with the cytoplasmic tail of the CD4 antigen. Murine p56lck can interact across species with the human CD4 receptor. Furthermore, peptide competition studies showed that a specific sequence within the cytoplasmic tail of CD4 interacts with the kinase. Cysteine residues also appear to play key roles in this interaction. Lastly, we show biochemically that the CD4:p56lck complex can physically associate with the epsilon chain of the CD3 complex on HPB-ALL transformed T cells. This interaction may provide a bridge by which events related to ligand binding to Ti(TcR)/CD3 may trigger T cells via the CD4/CD8:p56lck complex.
Rudd
C E
CE
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Barber
E K
EK
Burgess
K E
KE
Hahn
J Y
JY
Odysseos
A D
AD
Sy
M S
MS
Schlossman
S F
SF
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D017252:CD3 Complex; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)