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Updated: Aug 8, 2026
Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
Published on: March 10, 2021
Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both
E Degen1, M F Cohen-Doyle, D B Williams
1Department of Biochemistry, University of Toronto, Ontario, Canada.
Insights
The 88-kD protein (p88) retains incompletely assembled major histocompatibility complex class I molecules in the endoplasmic reticulum. Efficient dissociation requires beta 2-microglobulin and peptide binding for proper transport.
Area of Science:
- Immunology
- Cell Biology
- Protein Biochemistry
Background:
- An 88-kD protein (p88) binds newly synthesized murine major histocompatibility complex class I molecules in the endoplasmic reticulum (ER).
- p88 dissociation is a rate-limiting step for class I transport from the ER to the Golgi apparatus.
Purpose of the Study:
- To investigate the relationship between p88 interaction and the assembly of the ternary complex of class I heavy chain, beta 2-microglobulin (beta 2m), and peptide ligand.
- To elucidate the role of p88 in the retention and transport of major histocompatibility complex class I molecules.
Main Methods:
- Analysis of p88 association with major histocompatibility complex class I molecules in beta 2m-deficient murine and human cells.
- Examination of p88 interaction with "empty" class I heterodimers in murine RMA-S cells defective in peptide loading.
Main Results:
- In beta 2m-deficient cells, p88 remained associated with intracellular heavy chains, and transport was significantly impaired.
- In RMA-S cells, p88 showed prolonged association with "empty" heterodimers, correlating with slow ER to Golgi transport.
- A strong correlation was observed between p88 association and impaired class I transport.
Conclusions:
- p88 functions to retain incompletely assembled major histocompatibility complex class I molecules within the ER.
- Conformational changes in class I heavy chains, induced by beta 2m and peptide binding, are crucial for p88 dissociation and subsequent transport.
Abstract:
Previously, we showed that an 88-kD protein (p88) associates rapidly and quantitatively with newly synthesized murine major histocompatibility complex class I molecules within the endoplasmic reticulum (ER). This interaction is transient and dissociation of p88 appears to be rate limiting for transport of class I molecules from the ER to the Golgi apparatus. In this report, we examine the relationship between p88 interaction and assembly of the ternary complex of class I heavy chain beta 2-microglobulin (beta 2m), and peptide ligand. In both murine and human beta 2m-deficient cells, in which little or no transport of class I heavy chains is observed, p88 remained associated with intracellular heavy chains throughout their lifetime. In murine RMA-S cells, which are apparently defective in accumulating peptide ligands for class I within the ER, prolonged association of p88 with "empty" heavy chain-beta 2m heterodimers was also observed. However, p88 dissociated slowly in parallel with the slow rate of ER to Golgi transport of empty class I molecules in these cells. The close correlation between p88 association and impaired class I transport suggests that p88 functions to retain incompletely assembled class I molecules in the ER. We propose that conformational changes in class I heavy chains induced by the binding of both beta 2m and peptide are required for efficient p88 dissociation and subsequent class I transport.
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