Dissociation of β2m from MHC class I triggers formation of noncovalent transient heavy chain dimers

Cindy Dirscherl, Sara Löchte, Zeynep Hein, Janine Denise Kopicki, Antonia Regina Harders, Noemi Linden, Andreas Karner, Johannes Preiner, Julian Weghuber, Maria Garcia-Alai, Charlotte Uetrecht, Martin Zacharias, Jacob Piehler, Peter Lanzerstorfer, Sebastian Springer

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

At the plasma membrane of mammalian cells, major histocompatibility complex class I molecules (MHC-I) present antigenic peptides to cytotoxic T cells. Following the loss of the peptide and the light chain beta-2 microglobulin (β2m, encoded by B2M), the resulting free heavy chains (FHCs) can associate into homotypic complexes in the plasma membrane. Here, we investigate the stoichiometry and dynamics of MHC-I FHCs assemblies by combining a micropattern assay with fluorescence recovery after photobleaching (FRAP) and with single-molecule co-tracking. We identify non-covalent MHC-I FHC dimers, with dimerization mediated by the α3 domain, as the prevalent species at the plasma membrane, leading a moderate decrease in the diffusion coefficient. MHC-I FHC dimers show increased tendency to cluster into higher order oligomers as concluded from an increased immobile fraction with higher single-molecule colocalization. In vitro studies with isolated proteins in conjunction with molecular docking and dynamics simulations suggest that in the complexes, the α3 domain of one FHC binds to another FHC in a manner similar to that seen for β2m.

Original languageEnglish
Article numberjcs259498
JournalJournal of Cell Science
Volume135
Issue number9
DOIs
StatePublished - May 2022
Externally publishedYes

Keywords

  • Antigen presentation
  • MHC-I
  • Major histocompatibility complex class I
  • Protein oligomerization

Fingerprint

Dive into the research topics of 'Dissociation of β2m from MHC class I triggers formation of noncovalent transient heavy chain dimers'. Together they form a unique fingerprint.

Cite this