Dissociation of β2-microglobulin determines the surface quality control of major histocompatibility complex class I molecules

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Sebastián MontealegreSebastian Springer

Abstract

Major histocompatibility complex class I proteins, which present antigenic peptides to cytotoxic T lymphocytes at the surface of all nucleated cells, are endocytosed and destroyed rapidly once their peptide ligand has dissociated. The molecular mechanism of this cellular quality control process, which prevents rebinding of exogenous peptides and thus erroneous immune responses, is unknown. To identify the nature of the decisive step in endocytic sorting of class I molecules and its location, we have followed the removal of optimally and suboptimally peptide-loaded murine H-2K(b) class I proteins from the cell surface. We find that the binding of their light chain, β2-microglobulin (β2m), protects them from endocytic destruction. Thus, the extended survival of suboptimally loaded K(b) molecules at 25°C is attributed to decreased dissociation of β2m. Because all forms of K(b) are constantly internalized but little β2m-receptive heavy chain is present at the cell surface, it is likely that β2m dissociation and recognition of the heavy chain for lysosomal degradation take place in an endocytic compartment.

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Citations

Mar 17, 2015·Current Opinion in Immunology·Sebastian Springer
Mar 16, 2017·ACS Applied Materials & Interfaces·Tatiana A KolesnikovaMathias Winterhalter
Sep 25, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Myriam LawandPeter van Endert
Nov 20, 2019·Life Science Alliance·Sebastian MontealegrePeter van Endert
Jun 21, 2016·Immunological Reviews·Peter van Endert
Jan 23, 2019·Frontiers in Immunology·Sebastian Montealegre, Peter M van Endert

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