International Immunology, Vol. 11, No. 9, 1395-1401,
September 1999
© 1999 Japanese Society for Immunology
Translocation of tyrosine-phosphorylated TCR
chain to glycolipid-enriched membrane domains upon T cell activation
School of Allied Health Sciences, Faculty of Medicine Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan
1 Biomedical Research Center, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
2 Department of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa 259-1141, Japan.
Correspondence to: : A. Kosugi
Recent studies point to glycolipid-enriched membrane (GEM) microdomains as the critical sites for TCR-mediated signal transduction. However, whether the TCR complex is localized in the GEM domain is not well-defined. In the present study, we analyzed localization of the TCR–CD3 complex in the GEM domain by isolating the GEM fraction with sucrose density gradient centrifugation. Although 10% of TCR
chains was localized in the GEM fraction, most of the TCR complexes were excluded from the GEM before and after T cell activation, and the amount of TCR in the GEM was not increased after activation. However, the tyrosine-phosphorylated form of TCR was strongly concentrated in the GEM fraction upon TCR engagement. A kinetic study revealed that tyrosine phosphorylation of TCR occurred initially in the Triton X-100-soluble membrane fraction followed by the accumulation of phosphorylated TCR in the GEM. Thus, these results indicate that phosphorylated TCR migrates into the GEM domains on T cell activation. We speculate that the GEM microdomains may function as a reservoir of activation signals from triggered TCR.
Keywords: glycolipid-enriched membrane, microdomain, phosphorylation, TCR, TCR chain
The first two authors contributed equally to this work
Transmitting editor: A. Singer
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