Asset Details
Do you wish to reserve the book?
MHC class II complexes sample intermediate states along the peptide exchange pathway
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
MHC class II complexes sample intermediate states along the peptide exchange pathway
Do you wish to request the book?
MHC class II complexes sample intermediate states along the peptide exchange pathway
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
MHC class II complexes sample intermediate states along the peptide exchange pathway
2016
Overview
The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR-detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII’s ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual’s MHC restricted immune response.
MHCII proteins bind and present both foreign and self-antigens to potentially activate CD4+ T cells via cognate T cell receptors (TCRs) during the adaptive immune response. Here, the authors combine NMR-detected H/D exchange with Markov modelling analysis to shed light on the dynamics of MHCII peptide exchange.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82
/ 82/103
/ 82/83
/ Animals
/ Antigen Presentation - immunology
/ Histocompatibility antigen HLA
/ Histocompatibility Antigens Class II - chemistry
/ Histocompatibility Antigens Class II - immunology
/ Histocompatibility Antigens Class II - metabolism
/ Humanities and Social Sciences
/ Humans
/ Kinetics
/ Magnetic Resonance Spectroscopy
/ Major histocompatibility complex
/ Molecular Dynamics Simulation
/ NMR
/ Peptides
/ Science
