Association of CD8 with p56lck is required for early T cell signalling events

• Published in: The EMBO journal Vol. 10; no. 5; pp. 1201 - 1207
• Main Authors: Chalupny, N. J., Ledbetter, J. A., Kavathas, P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-05-1991
• Subjects: Amino Acid Sequence; Analysis of the immune response. Humoral and cellular immunity; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Binding Sites; Biological and medical sciences; Calcium - metabolism; CD8 Antigens; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycoproteins - genetics; Glycoproteins - immunology; Humans; Immunobiology; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Mutagenesis, Site-Directed; Organs and cells involved in the immune response; Phosphorylation; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - immunology; Signal Transduction - immunology; T-Lymphocytes - immunology; Transfection; Human; Cell culture; Flow cytometry; Enzyme; Leukemia; Activation; Binding site; Signal transduction; Cell line; Mutagenesis; T-Lymphocyte; Molecular association; Immunoblotting assay; Protein-tyrosine kinase
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1991.tb08061.x

The human CD8 glycoprotein functions as a co‐receptor during T cell activation by both binding to MHC class I and transducing a transmembrane signal. The ability of CD8 to transduce a signal is mediated in part by its association with the protein tyrosine kinase p56lck. Using a panel of human CD8 alpha mutants, we demonstrated that the presence of a functional p56lck binding site is required for the early signalling events transduced by CD8, including increased [Ca2+]i and protein tyrosine phosphorylation. In addition, our results demonstrate that wild‐type and all mutant forms of CD8 alpha have an inhibitory effect on signal transduction after CD3‐CD3 or CD3‐CD4 crosslinking when transfected into the (CD3+, CD4+, CD8‐) H9 T cell line, suggesting that intermolecular associations of CD8, independent of its association with p56lck, are responsible for this effect. Signalling through CD4 or CD8 in a double positive thymocyte may therefore be different than in a single positive thymocyte or mature T cell.