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Un papel crítico para la tapasina en el ensamblaje y la función de los complejos multiméricos MHC clase I-TAP
B Ortmann1, J Copeman, P J Lehner
1Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.
Science (New York, N.Y.)
|August 29, 1997
Resumen
La tapasina es una proteína crucial que facilita la interacción entre las moléculas del complejo mayor de histocompatibilidad (MHC) clase I y el transportador asociado con el procesamiento de antígenos (TAP). Su expresión restaura la presentación normal de antígenos y el reconocimiento de células inmunes en células deficientes.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- Las moléculas del complejo mayor de histocompatibilidad (MHC) clase I presentan antígenos a los linfocitos T citotóxicos.
- El transportador asociado con el procesamiento de antígenos (TAP) es esencial para cargar péptidos en moléculas de clase I del MHC.
- La tapasina actúa como un puente molecular entre el MHC clase I y el TAP en el retículo endoplasmático.
Objetivo del estudio:
- Investigar el papel de la tapasina en el ensamblaje y la función de los complejos de carga de péptidos de clase I del MHC.
- Para caracterizar las propiedades moleculares e interacciones de la tapasina.
- Determinar la importancia funcional de la tapasina en la presentación de antígenos y el reconocimiento de células T.
Principales métodos:
- Clonación molecular y caracterización del gen de la tapasina.
- Análisis de las interacciones proteína-proteína utilizando ensayos de coinmunoprecipitación.
- Estudios funcionales en una línea celular mutante con deficiencia de tapasina (220).
- Evaluación de la expresión superficial de MHC clase I y el reconocimiento de células T citotóxicas.
Principales resultados:
- Tapasin es una glicoproteína transmembrana codificada por un gen ligado al MHC y pertenece a la superfamilia de las inmunoglobulinas.
- La tapasina forma complejos estables con moléculas MHC clase I y se une al TAP.
- La expresión de tapasina en 220 células restauró la asociación MHC clase I-TAP y la expresión superficial.
- La expresión de tapasina corrigió el reconocimiento defectuoso de las células infectadas por el virus por las células T citotóxicas.
Conclusiones:
- La tapasina juega un papel crítico en el ensamblaje y la función del complejo de carga de péptidos de clase I del MHC.
- La tapasina es esencial para el procesamiento y la presentación eficientes de antígenos restringidos de la clase I de CMH.
- Tapasin es indispensable para la vigilancia inmune adecuada por los linfocitos T citotóxicos.
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