Effector and regulatory T cells derived from the same T cell clone differ in MHC class II-peptide multimer binding.
MHC class II-peptide multimers are a valuable tool for antigen-specific detection of CD4(+) T cells. However, it has been proposed that T cells in a hypo-responsive state can have diminished binding of such multimers. In the present study, we investigated this phenomenon at the clonal level. We found that anergic CD4(+) T cells had a reduced capacity to bind MHC class II-peptide multimers compared to their non-anergic counterparts. Increasing the incubation temperature, time, or MHC-peptide valency could not equalize multimer binding by anergic and non-anergic T cells. Neither anergic T cells nor non-anergic T cells internalized the MHC class II-peptide dimers efficiently, and in both cases the dimers bound to the plasma membrane at locations containing a low amount of raft-associated lipids. Disruption of lipid rafts, however, led to decreased dimer binding by non-anergic T cells and to a lesser extent by anergic T cells. Finally, we show that the depth of the anergic state of the T cell, which determines its ability to regulate other T cell responses, correlates with the reduced dimer binding. We here demonstrate for the first time differential MHC class II-peptide multimer binding by regulatory (anergic) and effector T cells with identical TCR.
Nolte-'t Hoen
Esther N M
EN
Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Amoroso
Maria Grazia
MG
Veenstra
Jetty
J
Grosfeld-Stulemeyer
Mayken C
MC
van Eden
Willem
W
Broeren
Chris P M
CP
Wauben
Marca H M
MH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019281:Dimerization; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008081:Liposomes / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D008081:Liposomes; D010446:Peptide Fragments