title: Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
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.
authors.affiliation: Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Nadia
authors.initials: N
authors.lastname: Anikeeva
authors.forename: Dimitry
authors.initials: D
authors.lastname: Gakamsky
authors.forename: Jørgen
authors.initials: J
authors.lastname: Schøller
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sykulev
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D017634:Self Tolerance / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011948:Receptors, Antigen, T-Cell