Endogenous viral antigen processing generates pepvtide-specific MHC class I cell-surface clusters

Xiuju Lu, James S. Gibbs, Heather D. Hickman, Alexandre David, Brian P. Dolan, Yetao Jin, David M. Kranz, Jack R. Bennink, Jonathan W. Yewdell, Rajat Varma

Research output: Contribution to journalArticlepeer-review


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 Kb class I molecules segregate into preformed, long-lasting (hours) clusters on the antigen-presenting cell surface based on their bound viral peptide. Peptide-specific Kb clustering occurs when source antigens are expressed by vaccinia or vesicular stomatitis virus, either as proteasome-liberated precursors or free intracellular peptides. By contrast, Kb-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 Kb 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 Kb presents endogenous SIINFEKL more efficiently than tailless Kb. We propose that endogenous processing generates peptide-specific clusters of class I molecules to maximize the sensitivity and speed of T-cell immunosurveillance.

Original languageEnglish (US)
Pages (from-to)15407-15412
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - Sep 18 2012


  • Antigen processing/presentation
  • CD8 T cell recognition
  • Dual-color TIRF imaging
  • Intracellular trafficking
  • MHC class I clustering

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Endogenous viral antigen processing generates pepvtide-specific MHC class I cell-surface clusters'. Together they form a unique fingerprint.

Cite this