Your browser doesn't support javascript.
loading
Endogenous viral antigen processing generates peptide-specific MHC class I cell-surface clusters.
Lu, Xiuju; Gibbs, James S; Hickman, Heather D; David, Alexandre; Dolan, Brian P; Jin, Yetao; Kranz, David M; Bennink, Jack R; Yewdell, Jonathan W; Varma, Rajat.
Afiliación
  • Lu X; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A ; 109(38): 15407-12, 2012 Sep 18.
Article en En | MEDLINE | ID: mdl-22949678
Sensitivity is essential in CD8+ T-cell killing of virus-infected cells and tumor cells. Although the affinity of the T-cell receptor (TCR) for antigen is relatively low, the avidity of T cell-antigen-presenting cell interactions is greatly enhanced by increasing the valence of the interaction. It is known that TCRs cluster into protein islands after engaging their cognate antigen (peptides bound to MHC molecules). Here, we show that mouse K(b) class I molecules segregate into preformed, long-lasting (hours) clusters on the antigen-presenting cell surface based on their bound viral peptide. Peptide-specific K(b) clustering occurs when source antigens are expressed by vaccinia or vesicular stomatitis virus, either as proteasome-liberated precursors or free intracellular peptides. By contrast, K(b)-peptide complexes generated by incubating cells with synthetic peptides are extensively intermingled on the cell surface. Peptide-specific complex sorting is first detected in the Golgi complex, and compromised by removing the K(b) cytoplasmic tail. Peptide-specific clustering is associated with increased T-cell sensitivity: on a per-complex basis, endogenous SIINFEKL activates T cells more efficiently than synthetic SIINFEKL, and wild-type K(b) presents endogenous SIINFEKL more efficiently than tailless K(b). We propose that endogenous processing generates peptide-specific clusters of class I molecules to maximize the sensitivity and speed of T-cell immunosurveillance.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Péptidos / Antígenos de Histocompatibilidad Clase I / Antígenos Virales Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Péptidos / Antígenos de Histocompatibilidad Clase I / Antígenos Virales Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos