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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
36
3-POS
Board 3
Peptide Tuning of MHC Protein Energy Landscapes: A Key Aspect of Antigen
Presentation and Recognition in the Immune System
Cory Ayres,
Brian Baker
.
University of Notre Dame, Notre Damne, IN, USA.
Major histocompatibility complex (MHC) proteins bind and "present" peptides for recognition
by T cells of the immune system. Through a combination of structural biology and solution
biophysics, we previously demonstrated that different peptides “tune” the energy landscapes of
MHC proteins. The consequences of this tuning on the motional properties of MHC proteins
impacts recognition by T cell receptors of the immune system. To explore this phenomenon in
more detail, here we describe the creation and analysis of a large library of molecular simulations
of different peptides bound to the most common class I MHC protein, HLA-A2. Nearly 100
different peptide/HLA-A2 complexes were simulated for 1 microsecond, generating a rich
dataset of MD data for the same protein bound to different peptides. We identified key residues
that are important in tuning of HLA-A2 dynamics and show that the HLA-A2 energy landscape
is modulated such that protein dynamics are altered across the protein. Altered dynamics are
transmitted not only to sites that interact with T cell receptors, but sites that interact with other
activating and inhibitory immune receptors and components of the peptide loading and editing
machinery. We propose that modulation of the energy landscape of MHC proteins is a key aspect
of antigen presentation and recognition in the immune system.