Close proximity between ICAM-1 and agonist pMHC-I ligands facilitates T cell integrin activation advancing local cytoskeleton remodeling (TECH1P.856)

Abstract

Abstract To mimic clustering of ICAM-1 and pMHC-I molecules, we assembled pMHC-I and ICAM-1 proteins on fluorescent nanoparticles (NP) and compared the binding of ICAM-1/NP, pMHC/NP and ICAM-1/pMHC-I/NP conjugates to live T cells. The binding of the ICAM-1/NP was poor, but it has been significantly enhanced in the presence of Mg2+ that induce high-affinity conformation of LFA-1. The addition of agonist pMHC-I/NP or anti-CD3 antibody did not influence the binding of the ICAM-1/NP to the T cells. However, when both agonist pMHC-I and ICAM-1 were assembled on NP, a profound increase in the binding of the ICAM-1/pMHC-I/NP was observed. The amplification effect was non-additive suggesting that ICAM-1 and pMHC-I displayed on the NP cooperate in their binding to TCR and LFA-1 on T cells. In control experiment, NP bearing ICAM-1 and null pMHC did not reveal the cooperative binding to the T cells. We conclude that the close proximity of agonist pMHC-I and ICAM-1 facilitates conversion of LFA-1 to a high affinity form upon productive TCR engagement. We propose that this cooperative affect advances initial local cytoskeleton remodeling enhancing the sensitivity and kinetics of TCR signaling.