The human class II MHC protein HLA-DR1 assembles as empty αβ heterodimers in the absence of antigenic peptide

doi:10.1016/0092-8674(92)90184-E

Cell

Volume 68, Issue 3, 7 February 1992, Pages 465-477

https://doi.org/10.1016/0092-8674(92)90184-E Get rights and content

Abstract

We have produced the human class II histocompatibility protein, HLA-DR1, as a soluble, secreted glycoprotein in insect cells infected with baculoviruses carrying truncated α and β subunit genes. The peptide-binding site is empty, and the empty molecules are fully competent to bind antigenic peptide. We used the empty molecules to measure an intrinsic rate for peptide association, and to investigate the role of peptide in stabilizing the class II structure. Peptide binding kinetics for the empty molecule are only 10-fold faster than for peptide exchange into an occupied site, suggesting that a conformational change may accompany peptide binding. The native αβ heterodimer assembles in the absence of antigenic peptide, but peptide binding stabilizes the empty heterodimer against aggregation and against SDS-induced denaturation.

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ArticleThe human class II MHC protein HLA-DR1 assembles as empty αβ heterodimers in the absence of antigenic peptide

Abstract

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Structure of the human class I histocompatibility antigen, HLA-A2

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Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes

Nature

The interaction between protein-derived immunogenic peptides and la

Immunol. Rev.

Autologous peptides constitutively occupy the antigen binding site on la

Science

Binding of labelled influenza matrix peptide to HLA DR in living B lymphoid cells

Nature

Direct binding of influenza peptides to class I HLA molecules

Nature

Biosynthesis and processing of class II histocompatibility antigens

CRC Crit. Rev. Immunol.

Asparagine-linked oligosaccharide processing in lepidopteran insect cells

Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 or recombinant human plasminogen produced in baculovirus vector-infected Spodoptera frugiperda (IPLB-SF-21AE) cells

Biochemistry

MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters

Nature

Refolding and reassembly of separate α and β chains of class II molecules of the major histocompatibility complex leads to increased peptide-binding capacity

Structural intermediates in the reactions of antigenic peptides with MHC molecules

Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules

Nature

MHC class II structure, occupancy and surface expression determined by post-endoplasmic reticulum antigen binding

Nature

A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC

Nature

Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment

Nature

Functional and ultrastructural evidence for intracellular formation of major histocompatibility complex class II-peptide complexes during antigen processing

Effect of secondary substrate binding in penicillopepsin: contributions of subsites S3 and S2′ to kcat

Biochemistry

Defective presentation of endogenous antigen by a cell line expressing class I molecules

Science

Article
The human class II MHC protein HLA-DR1 assembles as empty αβ heterodimers in the absence of antigenic peptide

Effect of secondary substrate binding in penicillopepsin: contributions of subsites S₃ and S₂′ to k_cat