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SLAMF6 clustering is required to augment T cell activation.
Dragovich, Matthew A; Adam, Kieran; Strazza, Marianne; Tocheva, Anna S; Peled, Michael; Mor, Adam.
Afiliación
  • Dragovich MA; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, United States of America.
  • Adam K; Division of Rheumatology, Columbia University Medical Center, New York, New York, United States of America.
  • Strazza M; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, United States of America.
  • Tocheva AS; Division of Rheumatology, Columbia University Medical Center, New York, New York, United States of America.
  • Peled M; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, United States of America.
  • Mor A; Division of Rheumatology, Columbia University Medical Center, New York, New York, United States of America.
PLoS One ; 14(6): e0218109, 2019.
Article en En | MEDLINE | ID: mdl-31199820
The signaling lymphocytic activation molecule (SLAM) family is comprised of nine distinct receptors that are expressed exclusively on hematopoietic cells. Most of these transmembrane receptors are homotypic by nature and downstream signaling occurs when cells that express the same SLAM receptor interact. Previous studies have determined that anti-SLAMF6 antibodies can have a therapeutic effect in autoimmunity and cancer. However, little is known about the role of SLAMF6 in the adaptive immune responses and in order to utilize SLAMF6 interventional approaches, a better understanding of the biology of this receptor in T cell is warranted. Accordingly, the objective of our study was to investigate both functionally and structurally the role of SLAMF6 in T cell receptor (TCR) mediated responses. Biochemical and genetic experiments revealed that SLAMF6 was required for productive TCR downstream signaling. Interestingly, SLAMF6 ectodomain was required for its function, but not for its recruitment to the immunological synapse. Flow-cytometry analysis demonstrated that tyrosine 308 of the tail of SLAMF6 was crucial for its ability to enhance T cell function. Imaging studies revealed that SLAMF6 clustering, specifically with the TCR, resulted in dramatic increase in downstream signaling. Mechanistically, we showed that SLAMF6 enhanced T cell function by increasing T cell adhesiveness through activation of the small GTPase Rap1. Taken together SLAMF6 is an important regulator of T cell activation where both its ectodomain and its endodomain contribute differentially to T cell functions. Additional studies are underway to better evaluate the role of anti-SLAMF6 approaches in specific human diseases.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T / Familia de Moléculas Señalizadoras de la Activación Linfocitaria Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T / Familia de Moléculas Señalizadoras de la Activación Linfocitaria Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos