Physical and functional association of LFA-1 with DNAM-1 adhesion molecule

K Shibuya; L L Lanier; J H Phillips; H D Ochs; K Shimizu; E Nakayama; H Nakauchi; A Shibuya

doi:10.1016/s1074-7613(00)80136-3

Physical and functional association of LFA-1 with DNAM-1 adhesion molecule

Immunity. 1999 Nov;11(5):615-23. doi: 10.1016/s1074-7613(00)80136-3.

Authors

K Shibuya¹, L L Lanier, J H Phillips, H D Ochs, K Shimizu, E Nakayama, H Nakauchi, A Shibuya

Affiliation

¹ Department of Immunology, Institute of Basic Medical Sciences, Center for TARA, University of Tsukuba, Japan.

PMID: 10591186
DOI: 10.1016/s1074-7613(00)80136-3

Abstract

Whereas ligation of the DNAM-1 adhesion molecule triggers cytotoxicity mediated by normal NK and T cells, this function was defective in NK cell clones from leukocyte adhesion deficiency syndrome. However, genetic reconstitution of cell surface expression of LFA-1 restored the ability of DNAM-1 to initiate anti-DNAM-1 mAb-induced cytotoxicity, indicating a functional relationship between DNAM-1 and LFA-1. Further studies demonstrated that LFA-1 physically associates with DNAM-1 in NK cells and anti-CD3 mAb stimulated T cells, for which serine phosphorylation of DNAM-1 plays a critical role. In addition, cross-linking of LFA-1 induces tyrosine phosphorylation of DNAM-1, for which the Fyn protein tyrosine kinase is responsible. These results indicate that DNAM-1 is involved in the LFA-1-mediated intracellular signals.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology
Antigens, Differentiation, T-Lymphocyte*
CD3 Complex / immunology
COS Cells
Cell Adhesion
Cell Adhesion Molecules / chemistry
Cell Adhesion Molecules / immunology
Cell Adhesion Molecules / physiology*
Chlorocebus aethiops
Cytotoxicity, Immunologic
Genetic Complementation Test
Humans
Jurkat Cells
Killer Cells, Natural / immunology
Leukocyte-Adhesion Deficiency Syndrome / immunology
Leukocyte-Adhesion Deficiency Syndrome / pathology*
Lymphocyte Activation
Lymphocyte Function-Associated Antigen-1 / chemistry
Lymphocyte Function-Associated Antigen-1 / physiology*
Mice
Phosphorylation
Phosphoserine / metabolism
Protein Processing, Post-Translational
Proto-Oncogene Proteins / physiology
Proto-Oncogene Proteins c-fyn
Signal Transduction / physiology*
T-Lymphocytes / immunology
Tumor Cells, Cultured

Substances

Antibodies, Monoclonal
Antigens, Differentiation, T-Lymphocyte
CD226 antigen
CD3 Complex
Cell Adhesion Molecules
Lymphocyte Function-Associated Antigen-1
Proto-Oncogene Proteins
Phosphoserine
FYN protein, human
Fyn protein, mouse
Proto-Oncogene Proteins c-fyn