Impact of lipid rafts on the-cell-receptor and peptide-major-histocompatibility-complex interactions under different measurement conditions
Open Access
- 10 January 2017
- journal article
- research article
- Published by American Physical Society (APS) in Physical Review E
- Vol. 95 (1), 012403
- https://doi.org/10.1103/physreve.95.012403
Abstract
The interactions between T-cell receptor (TCR) and peptide-major-histocompatibility complex (pMHC), which enable T-cell development and initiate adaptive immune responses, have been intensively studied. However, a central issue of how lipid rafts affect the TCR-pMHC interactions remains unclear. Here, by using a statistical-mechanical membrane model, we show that the binding affinity of TCR and pMHC anchored on two apposing cell membranes is significantly enhanced because of the lipid raft-induced signaling protein aggregation. This finding may provide an alternative insight into the mechanism of T-cell activation triggered by very low densities of pMHC. In the case of cell-substrate adhesion, our results indicate that the loss of lateral mobility of the proteins on the solid substrate leads to the inhibitory effect of lipid rafts on TCR-pMHC interactions. Our findings help to understand why different experimental methods for measuring the impact of lipid rafts on the receptor-ligand interactions have led to contradictory conclusions.Funding Information
- National Natural Science Foundation of China (11472285, 11232013, 11402193)
- Chinese Academy of Sciences (XDB22040102)
This publication has 75 references indexed in Scilit:
- Increased Cholesterol Content in Gammadelta (γδ) T Lymphocytes Differentially Regulates Their ActivationPLOS ONE, 2013
- The Role of Membrane Stiffness and Actin Turnover on the Force Exerted by DRG LamellipodiaBiophysical Journal, 2012
- T-cell triggering thresholds are modulated by the number of antigen within individual T-cell receptor clustersProceedings of the National Academy of Sciences of the United States of America, 2011
- Mechanisms for T cell receptor triggeringNature Reviews Immunology, 2010
- The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsivenessNature, 2010
- T Cell Receptor-Dependent Regulation of Lipid Rafts Controls Naive CD8+ T Cell HomeostasisImmunity, 2010
- TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activationNature Immunology, 2009
- Origin of the sharp boundary that discriminates positive and negative selection of thymocytesProceedings of the National Academy of Sciences of the United States of America, 2009
- Receptor-Independent, Direct Membrane Binding Leads to Cell-Surface Lipid Sorting and Syk Kinase Activation in Dendritic CellsImmunity, 2008
- T‐cell antigen receptor triggering and lipid rafts: a matter of space and time scalesEMBO Reports, 2008