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PMID: 1902413 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 10 ·No. 5 ·1991-05-00 ·Pages 1201-7

Chalupny NJ, Ledbetter JA, Kavathas P

Abstract

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.

MeSH Terms
Amino Acid Sequence Antigens, CD/genetics,immunology Antigens, Differentiation, T-Lymphocyte/genetics,immunology Binding Sites CD8 Antigens Calcium/metabolism Glycoproteins/genetics,immunology Humans Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Mutagenesis, Site-Directed Phosphorylation Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogene Proteins/chemistry,immunology Signal Transduction/immunology T-Lymphocytes/immunology Transfection
Chemicals
Antigens, CD Antigens, Differentiation, T-Lymphocyte CD8 Antigens Glycoproteins Proto-Oncogene Proteins Protein-Tyrosine Kinases Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chalupny N J
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510.
Ledbetter J A
Kavathas P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-05-00
Pages
1201-7
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452774
Subset
IM
Grants
NCI NIH HHS · CA 48115 · United States
External Links
PubMed source PMC Full Text View journal details
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