title: Impact of lipid rafts on the T-cell-receptor and peptide-major-histocompatibility-complex interactions under different measurement conditions.
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.
authors.affiliation: State Key Laboratory of Nonlinear Mechanics (LNM) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.affiliation: International Center for Applied Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi'an Jiaotong University, Xi'an, 710049, China.
authors.forename: Guang-Kui
authors.initials: GK
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Nonlinear Mechanics (LNM) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.|School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Song
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002448:Cell Adhesion; D003198:Computer Simulation; D004058:Diffusion; D008285:Major Histocompatibility Complex / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism*; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D010455:Peptides / Q000378:metabolism*; D066329:Protein Aggregates / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
chemical_list: D010455:Peptides; D066329:Protein Aggregates; D011948:Receptors, Antigen, T-Cell