Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.

Authors

Nadia Anikeeva, Thomas Jefferson UniversityFollow
Dimitry Gakamsky, Edinburgh Instruments Ltd., Livingston, United Kingdom
Jørgen Schøller, Immudex Inc., Copenhagen, Denmark
Yuri Sykulev, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

1-1-2012

Comments

This article has been peer reviewed. It was published in: PLoS One

2012; 7(8): e41466.

The published version is available at DOI: 10.1371/journal.pone.0041466. Copyright © PLoS One

Abstract

Noncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell receptor (TCR) and are always in a large access over the cognate pMHC on the surface of antigen presenting cells. We assembled soluble cognate and noncognate pMHC class I (pMHC-I) ligands at designated ratios on various scaffolds into oligomers that mimic pMHC clustering and examined how multivalency and density of the pMHCs in model clusters influences the binding to live CD8 T cells and the kinetics of TCR signaling. Our data demonstrate that the density of self pMHC-I proteins promotes their interaction with CD8 co-receptor, which plays a critical role in recognition of a small number of cognate pMHC-I ligands. This suggests that MHC clustering on live target cells could be utilized as a sensitive mechanism to regulate T cell responsiveness.

Recommended Citation

Anikeeva, Nadia; Gakamsky, Dimitry; Schøller, Jørgen; and Sykulev, Yuri, "Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling." (2012). Department of Microbiology and Immunology Faculty Papers. Paper 43.
https://jdc.jefferson.edu/mifp/43

PubMed ID

22870225