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La activación restringida por CD1d y mediada por TCR de las células NKT valpha14 por glicosilceramidas
1CREST (Core Research for Evolutional Science and Technology) Project, Japan Science and Technology Corporation (JST), 1-8-1 Inohana, Chuo, Chiba 260, Japan.
Science (New York, N.Y.)
|December 31, 1997
Resumen
Las células T Natural Killer (NKT) reconocen un ligando específico de glucosilceramida. Este reconocimiento implica vías compartidas con las células T y las células NK, destacando las interacciones únicas del sistema inmunológico.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Reconocimiento molecular.
Sus antecedentes:
- Los linfocitos T (NKT) asesinos naturales poseen un único y invariante receptor de antígeno de células T (TCR), Valpha14-Jalpha281.
- El ligando específico para este TCR invariante no se había identificado previamente.
Objetivo del estudio:
- Para identificar el ligando para el invariante Valpha14 TCR de la célula NKT.
- Aclarar los mecanismos moleculares y las vías celulares involucradas en la activación de las células NKT de Valpha14.
Principales métodos:
- Identificación de un nuevo ligando de glicosilceramida con longitudes de cadena específicas de acilo graso (C26) y esfingosina (C18).
- Evaluación de la proliferación celular Valpha14 NKT utilizando varios tratamientos inhibidores, incluyendo cloroquina-concanamicina A y anticuerpos dirigidos a las moléculas coestimuladoras (CD1d/Vbeta8, CD40/CD40L, B7/CTLA-4/CD28).
Principales resultados:
- Se identificó un nuevo ligando de glicosilceramida para el TCR de las células NKT de Valpha14.
- La proliferación inducida por la glicosilceramida de las células Valpha14 NKT fue bloqueada por inhibidores de la función lisosomal y anticuerpos contra las vías CD1d, CD40 y B7.
- La interferencia con las proteínas asociadas al transportador no afectó la respuesta proliferativa.
Conclusiones:
- La glucosilceramida identificada actúa como un ligando específico para el NKT invariante TCR.
- La activación de las células Valpha14 NKT por este ligando implica vías que se superponen con los sistemas de reconocimiento de células T y células NK.
- Esto sugiere un mecanismo de reconocimiento híbrido para las células NKT, distinto de las células T convencionales.
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