The MHC Class I Heavy Chain Structurally Conserved Cysteines 101 and 164 Participate in HLA-B27 Dimer Formation

2012 ◽  
Vol 16 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Izabela Lenart ◽  
David B. Guiliano ◽  
Garth Burn ◽  
Elaine C. Campbell ◽  
Kenneth D. Morley ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Hla B27 ◽  
Dimer Formation

scholarly journals Translocation of peptides through microsomal membranes is a rapid process and promotes assembly of HLA-B27 heavy chain and beta 2-microglobulin translated in vitro.

1991 ◽  
Vol 115 (4) ◽  
pp. 959-970 ◽  
Author(s):  
F Lévy ◽  
R Larsson ◽  
S Kvist
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Peptide Binding ◽  
Class I ◽  
Hla B27 ◽  
Heavy Chains ◽  
Microsomal Membranes ◽  
Beta 2 ◽  
Beta 2 Microglobulin

We have translated major histocompatibility complex (MHC) class I heavy chains and human beta 2-microglobulin in vitro in the presence of microsomal membranes and a peptide from the nucleoprotein of influenza A. This peptide stimulates assembly of HLA-B27 heavy chain and beta 2-microglobulin about fivefold. By modifying this peptide to contain biotin at its amino terminus, we could precipitate HLA-B27 heavy chains with immobilized streptavidin, thereby directly demonstrating class I heavy chain-peptide association under close to physiological conditions. The biotin-modified peptide stimulates assembly to the same extent as the unmodified peptide. Both peptides bind to the same site on the HLA-B27 molecule. Immediately after synthesis of the HLA-B27 heavy chain has been completed, it assembles with beta 2-microglobulin and peptide. These interactions occur in the lumen of the microsomes (endoplasmic reticulum), demonstrating that the peptide must cross the microsomal membrane in order to promote assembly. The transfer of peptide across the microsomal membrane is a rapid process, as peptide binding to heavy chain-beta 2-microglobulin complexes is observed in less than 1 min after addition of peptide. By using microsomes deficient of beta 2-microglobulin (from Daudi cells), we find a strict requirement of beta 2-microglobulin for detection of peptide interaction with the MHC class I heavy chain. Furthermore, we show that heavy chain interaction with beta 2-microglobulin is likely to precede peptide binding. Biotin-modified peptides are likely to become a valuable tool in studying MHC antigen interaction and assembly.

The murine gamma-herpesvirus-68 MK3 protein causes TAP degradation independent of MHC class I heavy chain degradation

2005 ◽  
Vol 35 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Jessica?M. Boname ◽  
Janet?S. May ◽  
Philip?G. Stevenson
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Gamma Herpesvirus

T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4930-4936 ◽  
Author(s):  
Lotta Hansson ◽  
Hodjattallah Rabbani ◽  
Jan Fagerberg ◽  
Anders Österborg ◽  
Håkan Mellstedt
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Heavy Chain ◽  
T Cell Response ◽  
Class I ◽  
Type I ◽  
T Cell Epitopes ◽  
Hla Binding

Abstract The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded as a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain (VH) in MM (n = 5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype-derived peptides. A large number of human-leukocyte-antigen (HLA)–binding (class I and II) peptides were identified. The frequency of predicted epitopes depended on the database used: 245 in bioinformatics and molecular analysis section (BIMAS) and 601 in SYFPEITHI. Most of the peptides displayed a binding half-life or score in the low or intermediate affinity range. The majority of the predicted peptides were complementarity-determining region (CDR)–rather than framework region (FR)–derived (52%-60% vs 40%-48%, respectively). Most of the predicted peptides were confined to the CDR2-FR3-CDR3 “geographic” region of the Ig-VH region (70%), and significantly fewer peptides were found within the flanking (FR1-CDR1-FR2 and FR4) regions (P < .01). There were 8– to 10–amino acid (aa) long peptides corresponding to the CDRs and fitting to the actual HLA-A/B haplotypes that spontaneously recognized, albeit with a low magnitude, type I T cells (interferon γ), indicating an ongoing major histocompatibility complex (MHC) class I–restricted T-cell response. Most of those peptides had a low binding half-life (BIMAS) and a low/intermediate score (SYFPEITHI). Furthermore, 15- to 20-aa long CDR1-3–derived peptides also spontaneously recognized type I T cells, indicating the presence of MHC class II–restricted T cells as well. This study demonstrates that a large number of HLA-binding idiotypic peptides can be identified in patients with MM. Such peptides may spontaneously induce a type I MHC class I– as well as class II–restricted memory T-cell response.

Isolation of a functional cDNA encoding the RT1.Au MHC class I heavy chain by a novel PCR-based method

1995 ◽  
Vol 41 (5) ◽  
Author(s):  
Etienne Joly ◽  
Carol Clarkson ◽  
JonathanC. Howard ◽  
GeoffreyW. Butcher
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Class I

scholarly journals The Pathway of Us11-Dependent Degradation of Mhc Class I Heavy Chains Involves a Ubiquitin-Conjugated Intermediate

1999 ◽  
Vol 147 (1) ◽  
pp. 45-58 ◽  
Author(s):  
Caroline E. Shamu ◽  
Craig M. Story ◽  
Tom A. Rapoport ◽  
Hidde L. Ploegh
Keyword(s):  
Mhc Class I ◽  
Heavy Chain ◽  
Control Process ◽  
Degradation Pathway ◽  
Cell System ◽  
Class I ◽  
Permeabilized Cell ◽  
Intact Cells ◽  
Heavy Chains ◽  
Quality Control Process

The human cytomegalovirus protein, US11, initiates the destruction of MHC class I heavy chains by targeting them for dislocation from the ER to the cytosol and subsequent degradation by the proteasome. We report the development of a permeabilized cell system that recapitulates US11-dependent degradation of class I heavy chains. We have used this system, in combination with experiments in intact cells, to identify and order intermediates in the US11-dependent degradation pathway. We find that heavy chains are ubiquitinated before they are degraded. Ubiquitination of the cytosolic tail of heavy chain is not required for its dislocation and degradation, suggesting that ubiquitination occurs after at least part of the heavy chain has been dislocated from the ER. Thus, ubiquitination of the heavy chain does not appear to be the signal to start dislocation. Ubiquitinated heavy chains are associated with membrane fractions, suggesting that ubiquitination occurs while the heavy chain is still bound to the ER membrane. Our results support a model in which US11 co-opts the quality control process by which the cell destroys misfolded ER proteins in order to specifically degrade MHC class I heavy chains.

scholarly journals Inhibition of Heavy Chain and β2-Microglobulin Synthesis as a Mechanism of Major Histocompatibility Complex Class I Downregulation during Epstein-Barr Virus Replication

2006 ◽  
Vol 81 (3) ◽  
pp. 1390-1400 ◽  
Author(s):  
Andre Ortlieb Guerreiro-Cacais ◽  
Mehmet Uzunel ◽  
Jelena Levitskaya ◽  
Victor Levitsky
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Heavy Chain ◽  
Epstein Barr Virus ◽  
Class I ◽  
Heavy Chains ◽  
Barr Virus ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Epstein Barr

ABSTRACT The mechanisms of major histocompatibility complex (MHC) class I downregulation during Epstein-Barr virus (EBV) replication are not well characterized. Here we show that in several cell lines infected with a recombinant EBV strain encoding green fluorescent protein (GFP), the virus lytic cycle coincides with GFP expression, which thus can be used as a marker of virus replication. EBV replication resulted in downregulation of MHC class II and all classical MHC class I alleles independently of viral DNA synthesis or late gene expression. Although assembled MHC class I complexes, the total pool of heavy chains, and β2-microglobulin (β2m) were significantly downregulated, free class I heavy chains were stabilized at the surface of cells replicating EBV. Calnexin expression was increased in GFP+ cells, and calnexin and calreticulin accumulated at the cell surface that could contribute to the stabilization of class I heavy chains. Decreased expression levels of another chaperone, ERp57, and TAP2, a transporter associated with antigen processing and presentation, correlated with delayed kinetics of MHC class I maturation. Levels of both class I heavy chain and β2m mRNA were reduced, and metabolic labeling experiments demonstrated a very low rate of class I heavy chain synthesis in lytically infected cells. MHC class I and MHC class II downregulation was mimicked by pharmacological inhibition of protein synthesis in latently infected cells. Our data suggest that although several mechanisms may contribute to MHC class I downregulation in the course of EBV replication, inhibition of MHC class I synthesis plays the primary role in the process.

scholarly journals Natural MHC Class I Polymorphism Controls the Pathway of Peptide Dissociation from HLA-B27 Complexes

2007 ◽  
Vol 93 (8) ◽  
pp. 2743-2755 ◽  
Author(s):  
Kathrin Winkler ◽  
Anja Winter ◽  
Christine Rueckert ◽  
Barbara Uchanska-Ziegler ◽  
Ulrike Alexiev
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Hla B27 ◽  
Peptide Dissociation
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