Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells.
J Immunol
; 200(4): 1471-1479, 2018 02 15.
Article
en En
| MEDLINE
| ID: mdl-29335257
ABSTRACT
Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein-coupled receptor (GPCR) leading to PLCß activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens. Complementary binding assays (ELISA, pull-downs, and surface plasmon resonance) provided direct evidence of the interaction between staphylococcal enterotoxin E and LAMA2. Through its G4 domain, LAMA2 mediated the LCK-independent T cell activation by these toxins. Such a coreceptor role of LAMA2 involved a GPCR of the calcium-sensing receptor type because the selective antagonist NPS 2143 inhibited superantigen-induced T cell activation in vitro and delayed the effects of toxic shock syndrome in vivo. Collectively, our data identify LAMA2 as a target of antagonists of staphylococcal superantigens to treat toxic shock syndrome.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Infecciones Estafilocócicas
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Activación de Linfocitos
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Linfocitos T
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Laminina
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Enterotoxinas
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá