Effector and regulatory T cells derived from the same T cell clone differ in MHC class II-peptide multimer binding
✍ Scribed by Esther N. M. Nolte-‘t Hoen; Maria Grazia Amoroso; Jetty Veenstra; Mayken C. Grosfeld-Stulemeyer; Willem van Eden; Chris P. M. Broeren; Marca H. M. Wauben
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 309 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
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.