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.
Programs in the National Natural Science Foundation of China [11472285, 11232013, 11402193]
; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB22040102]
; National Key Research and Development Program of China [2016YFA0501601]
[Li, Long; Song, Fan] Chinese Acad Sci, State Key Lab Nonlinear Mech LNM, Beijing 100190, Peoples R China; [Li, Long; Song, Fan] Chinese Acad Sci, Beijing Key Lab Engn Construct & Mechanobiol, Inst Mech, Beijing 100190, Peoples R China; [Xu, Guang-Kui] Xi An Jiao Tong Univ, Sch Aerosp, State Key Lab Strength & Vibrat Mech Struct, Int Ctr Appl Mech, Xian 710049, Peoples R China; [Song, Fan] Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China