LFA-1-dependent lipid raft recruitment of DNAM-1 (CD226) in CD4+ T cell

• Published in: International immunology Vol. 18; no. 6; pp. 951 - 957
• Main Authors: Shirakawa, Jun, Wang, Yinan, Tahara-Hanaoka, Satoko, Honda, Shin-ichiro, Shibuya, Kazuko, Shibuya, Akira
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2006; Oxford Publishing Limited (England)
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; DNAM-1; Gene Expression - genetics; Gene Expression - immunology; Humans; LFA-1; lipid rafts; Lymphocyte Function-Associated Antigen-1 - genetics; Lymphocyte Function-Associated Antigen-1 - immunology; Membrane Microdomains - immunology; Mice; Mice, Knockout; Phosphorylation; Protein Binding - genetics; Protein Binding - immunology; Protein Processing, Post-Translational - immunology; Protein Structure, Tertiary - genetics; Protein Transport - genetics; Protein Transport - immunology; Receptors, Antigen, T-Cell - immunology; Signal Transduction - genetics; Signal Transduction - immunology; T cell activation
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxl031

Upon antigen recognition by the TCR, both the leukocyte adhesion molecules DNAM-1 and leukocyte function-associated antigen-1 (LFA-1) associate with lipid rafts and form peripheral supra-molecular activation clusters that surround central-supra-molecular activation clusters at the immunological synapse. The serine residue in the cytoplasmic tail of DNAM-1 is responsible for this association of DNAM-1 with lipid rafts. The TCR-mediated signal also induces physical association of DNAM-1 with LFA-1, for which the serine phosphorylation of DNAM-1 is also responsible. However, how the serine residue is involved in lipid raft recruitment of DNAM-1 has remained unclear. Here, we show that, although the TCR-mediated signal induced the serine phosphorylation of DNAM-1, DNAM-1 did not associate with lipid rafts in CD4+ T cells derived from mice deficient in LFA-1 expression, indicating that lipid raft recruitment of DNAM-1 depends on LFA-1 expression. These results suggest that the serine phosphorylation of DNAM-1 primarily induces physical association of DNAM-1 with LFA-1, which then takes DNAM-1 into lipid raft compartment.