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Reconocimiento de células T de un epítopo de proteína básica de mielina inmunodominante en la esclerosis múltiple
1Division of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
Nature
|July 12, 1990
Resumen
Los investigadores identificaron una región específica de proteína básica de mielina (residuos 84-102) que es más frecuentemente atacada por las células T en pacientes con esclerosis múltiple (EM), particularmente aquellos con el fenotipo DR2. Este hallazgo puede explicar la patogénesis de la EM en algunos individuos.
Área de la Ciencia:
- Neuroinmunología La neuroinmunología.
- Enfermedades autoinmunes Las enfermedades autoinmunes.
- Trastornos del sistema nervioso central Trastornos del sistema nervioso central
Sus antecedentes:
- La esclerosis múltiple (EM) es una enfermedad autoinmune del sistema nervioso central.
- Las células T que se dirigen a los antígenos de la mielina están implicadas en la patogénesis de la EM.
- Las asociaciones de clase II del complejo mayor de histocompatibilidad (MHC), como DR2, sugieren la participación del sistema inmunológico.
Objetivo del estudio:
- Para definir la especificidad de las células T hacia la proteína básica de mielina (MBP) en la esclerosis múltiple.
- Investigar la asociación entre la reactividad de las células T a regiones específicas de MBP y los fenotipos de MHC clase II.
Principales métodos:
- Se establecieron 15.824 líneas de células T a corto plazo de pacientes con EM, otros pacientes con enfermedades neurológicas y controles sanos.
- Se evaluó la reactividad de las células T contra los péptidos de proteína básica de mielina.
- Respuestas correlacionadas de células T con fenotipos de clase II del complejo mayor de histocompatibilidad (MHC) (DR2, DQw1, DRw11).
Principales resultados:
- Se encontró una mayor frecuencia de líneas de células T reactivas a la región MBP asociada a DR2 (residuos 84-102) en pacientes con EM en comparación con los controles.
- Se reconoció una segunda región de MBP (residuos 143-168) igualmente en pacientes con EM y controles, asociada con el fenotipo DRw11.
- El péptido inmunodominante 84-102 fue restringido tanto por DR2 como por DQw1, y estas asociaciones se observaron en miembros de la familia.
Conclusiones:
- La región asociada a DR2 de la proteína básica de mielina (residuos 84-102) es un objetivo clave para las células T en pacientes con esclerosis múltiple con el fenotipo DR2.
- Esta región inmunodominante puede desempeñar un papel encefalitogénico en el desarrollo de la EM en individuos susceptibles.
- Comprender la especificidad de las células T y las asociaciones de MHC proporciona información sobre los mecanismos autoinmunes de la EM.
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