Dynamical Peptide Motions in MHC Groove is Crucial for Recognition and Activation of Certain T Cells

Abstract

We detected dynamic motions of peptides in MHC II with single-molecule technology using X-rays. T cells see peptides in the context of MHC molecules. This recognition should be specific to each antigens to prevent anomalous self-attack by the activated T cells. However, cross-reactivity of T cell is also well known phenomena. Also, some T cells see peptides/MHC in peculiar forms. As a typical of such peptide/MHC, we studied type B form of I-Ak with HEL peptides, as well as I-Ag7 with newly found diabetogenic peptides for molecular flexibility. in order to elucidate the mechanism of the recognition, we used diffracted X-ray tracking method (DXT) that monitors real-time movements of individual proteins in solution at the single-molecular level. We found that peptides have its individual Brownian motions that are different from MHC protein themself, and the extent of motion diminishes by time in order of days, which may mimic the DM function. We also found that the rotational motions of peptides correlate with the type B T cell activation or with diabetogenic I-Ag7 activation. The rotational motion of peptides may create transient conformation of peptide/MHC complex that recognized by a population of T cells.