Mediation by HLA-DM of dissociation of peptides from HLA-DR

Sloan, Victor S.; Cameron, Patricia M.; Porter, Gene; Gammon, Maureen C.; Amaya, Miguel; Mellins, Elizabeth; Zaller, Dennis M.

doi:10.1038/375802a0

Cited by 522 publications

(448 citation statements)

References 30 publications

Supporting

Mentioning

436

Contrasting

Order By: Relevance

“…Several models for the activity of the peptide exchange factor HLA-DM in catalyzing peptide exchange postulate a loosely bound class II MHC-peptide complex intermediate that interacts with HLA-DM (60)(61)(62)(63)(64)(65). If the correspondence between the kinetic mechanism and the conformational change observed here is correct, the kinetic intermediate retaining the conformation of the empty protein provides a handle for recognition by HLA-DM.…”

Section: Discussionmentioning

confidence: 99%

A Conformational Change in the Human Major Histocompatibility Complex Protein HLA-DR1 Induced by Peptide Binding

et al. 1999

View full text Add to dashboard Cite

To investigate a conformational change accompanying peptide binding to class II MHC proteins, we probed the structure of a soluble version of the human class II MHC protein HLA-DR1 in empty and peptide-loaded forms. Peptide binding induced a large decrease in the effective radius of the protein as determined by gel filtration, dynamic light scattering, and analytical ultracentrifugation. It caused a substantial increase in the cooperativity of thermal denaturation and induced alterations in MHC polypeptide backbone structure as determined by circular dichroism. These changes suggest a condensation of the protein around the bound peptide. An antibody specific for 58-69 preferentially bound the empty protein, indicating that the peptide-induced conformational change involves the -subunit helical region. The conformational change may have important implications for the mechanisms of intracellular antigen presentation pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

A Conformational Change in the Human Major Histocompatibility Complex Protein HLA-DR1 Induced by Peptide Binding

et al. 1999

View full text Add to dashboard Cite

show abstract

“…In MIICs, the exchange of CLIP for other peptides is facilitated by the nonclassical MHC molecule HLA-DM (H2-M in mice) (Denzin and Cresswell 1995;Sherman et al 1995;Sloan et al 1995;Kropshofer et al 1996;Weber et al 1996), but the degree of DM requirement for peptide loading is dependent on the MHCII isotype ( 2; additional symbols are indicated at the bottom. PRR signaling from phagosomes may stimulate selective recruitment of pMHCII from those compartments to the plasma membrane (bottom structure), hypothetically through interference with MHCII ubiquitination selectively at those phagosomes.…”

Section: Peptide Loading Onto Mhciimentioning

confidence: 99%

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

142

102

View full text Add to dashboard Cite

For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4 þ T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.

show abstract

“…Owing to substantial aggregation of this molecule, the more stable DQ2.5:DQ2.5-glia-v1 molecule was used in the remaining experiments. Soluble HLA-DM molecules were produced in stably transfected S2 cells and were purified by FLAG-tag immunoaffinity chromatography and size exclusion chromatography (22). …”

Section: Production Of Hla Affinity Matrices and Hla-dm Moleculesmentioning

confidence: 99%

HLA-DQ Molecules as Affinity Matrix for Identification of Gluten T Cell Epitopes

Dørum

Bodd

Fallang

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Even though MHC class II is a dominant susceptibility factor for many diseases, culprit T cell epitopes presented by disease-associated MHC molecules remain largely elusive. T cells of celiac disease lesions recognize cereal gluten epitopes presented by the disease-associated HLA molecules DQ2.5, DQ2.2, or DQ8. Employing celiac disease and complex gluten Ag digests as a model, we tested the feasibility of using DQ2.5 and DQ2.2 as an affinity matrix for identification of disease-relevant T cell epitopes. Known gluten T cell epitope peptides were enriched by DQ2.5, whereas a different set of peptides was enriched by DQ2.2. Of 86 DQ2.2-enriched peptides, four core sequences dominated. One of these core sequences is a previously known epitope and two others are novel epitopes. The study provides insight into the selection of gluten epitopes by DQ2.2. Furthermore, the approach presented is relevant for epitope identification in other MHC class II–associated disorders.

show abstract

Mediation by HLA-DM of dissociation of peptides from HLA-DR

Cited by 522 publications

References 30 publications

A Conformational Change in the Human Major Histocompatibility Complex Protein HLA-DR1 Induced by Peptide Binding

A Conformational Change in the Human Major Histocompatibility Complex Protein HLA-DR1 Induced by Peptide Binding

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

HLA-DQ Molecules as Affinity Matrix for Identification of Gluten T Cell Epitopes

Contact Info

Product

Resources

About