Journal
JOURNAL OF IMMUNOLOGY
Volume 168, Issue 5, Pages 2233-2239Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.168.5.2233
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI048189] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK054213] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI 48189] Funding Source: Medline
- NIDDK NIH HHS [DK 54213] Funding Source: Medline
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Lateral mobility and spatial organization of proteins within the plasma membrane are likely to mediate the initial events coordinating T cell activation. Lipid rafts, distinct cholesterol/sphingolipid-rich membrane microdomains, provide a mechanism for this regulation by concentrating or excluding signaling proteins. We demonstrate in peripheral blood T cell lymphoblasts that immediate early phosphotyrosine signal transduction through the TCR complex is functionally dependent on a distinct population of lipid rafts. Specifically, cholesterol extraction destabilizes the membrane microdomains containing Lck, while the rafts containing the adapter protein linker for activation of T cells remain intact. Heterogeneity in the partitioning of these proteins in resting cells was confirmed by immunoelectron microscopy. After T cell activation, both Lck and the linker for activation of T cells colocalize to 50-100 nm microdomains in the plasma membrane, indicating that sequestration of these proteins into distinct lipid rafts may function to regulate the initiation of T cell signal transduction.
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