scholarly journals Dynamic Flexibility of a Peptide-Binding Groove of Human HLA-DR1 Class II MHC Molecules: Normal Mode Analysis of the Antigen Peptide–Class II MHC Complex

2003 ◽  
Vol 51 (8) ◽  
pp. 923-928 ◽  
Author(s):  
Hiroyuki Nojima ◽  
Mayuko Takeda-Shitaka ◽  
Youji Kurihara ◽  
Kenshu Kamiya ◽  
Hideaki Umeyama
Keyword(s):  
Normal Mode ◽  
Normal Mode Analysis ◽  
Peptide Binding ◽  
Class Ii ◽  
Mode Analysis ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Antigen Peptide ◽  
Peptide Binding Groove ◽  
Binding Groove

PREDICTING PEPTIDE INTERACTIONS WITH MODEL CLASS II MHC STRUCTURES

2005 ◽  
Vol 14 (04) ◽  
pp. 561-575
Author(s):  
MARTIN T. SWAIN ◽  
ANTHONY J. BROOKS ◽  
GRAHAM J. L. KEMP
Keyword(s):  
Comparative Modeling ◽  
3D Models ◽  
Class Ii ◽  
Mhc Molecules ◽  
Automated Method ◽  
Class Ii Mhc ◽  
Peptide Interactions ◽  
Peptide Binding Groove ◽  
Binding Groove ◽  
Chain Conformations

An automated method for constructing 3D models of class II MHC structures that uses constraint logic programming to select side-chain conformations is described. This method follows a comparative modeling approach in basing the model structures on experimentally determined MHC-peptide structures, but it uses constraints to ease open the peptide binding groove so that the modeled MHC structure is a less specific fit for the co-crystallized peptide in the starting structure. The resulting models are used by a "peptide threading" program that attempts to predict peptides from a protein sequence that will bind strongly to particular MHC alleles. Our results indicate that MHC models that have been constructed in this way enable the peptide threading program to make binding predictions that are comparable with those obtained when using experimentally determined MHC structures, suggesting that a combined modeling and peptide threading approach is worth pursuing for MHC molecules for which experimentally determined structures are not available.

scholarly journals Implication of HLA-DMA Alleles in Corsican IDDM

1998 ◽  
Vol 14 (3) ◽  
pp. 135-141 ◽  
Author(s):  
P. Cucchi-Mouillot ◽  
S. Lai ◽  
C. Carcassi ◽  
P. Sorba ◽  
M. Stuart-Simoni ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Autoimmune Disease ◽  
Gene Polymorphism ◽  
Peptide Binding ◽  
Additional Tool ◽  
Classical Class ◽  
Antigen Peptide ◽  
Peptide Binding Groove ◽  
Binding Groove ◽  
Peptide Exchange

The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

Peptide binding by class I and class II MHC molecules

Biopolymers ◽  
1997 ◽  
Vol 43 (4) ◽  
pp. 281-302 ◽  
Author(s):  
Michael A. Batalia ◽  
Edward J. Collins
Keyword(s):  
Peptide Binding ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Class Ii Mhc

scholarly journals The Utility of Supertype Clustering in Prediction for Class II MHC-Peptide Binding

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3034 ◽  
Author(s):  
Wen-Jun Shen ◽  
Xun Zhang ◽  
Shaohong Zhang ◽  
Cheng Liu ◽  
Wenjuan Cui
Keyword(s):  
Computational Models ◽  
Peptide Binding ◽  
Class Ii ◽  
Antigenic Peptides ◽  
Dissimilarity Index ◽  
Binding Prediction ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Hla Dq ◽  
The Difference

Motivation: Extensive efforts have been devoted to understanding the antigenic peptides binding to MHC class I and II molecules since they play a fundamental role in controlling immune responses and due their involvement in vaccination, transplantation, and autoimmunity. The genes coding for the MHC molecules are highly polymorphic, and it is difficult to build computational models for MHC molecules with few know binders. On the other hand, previous studies demonstrated that some MHC molecules share overlapping peptide binding repertoires and attempted to group them into supertypes. Herein, we present a framework of the utility of supertype clustering to gain more information about the data to improve the prediction accuracy of class II MHC-peptide binding. Results: We developed a new method, called superMHC, for class II MHC-peptide binding prediction, including three MHC isotypes of HLA-DR, HLA-DP, and HLA-DQ, by using supertype clustering in conjunction with RLS regression. The supertypes were identified by using a novel repertoire dissimilarity index to quantify the difference in MHC binding specificities. The superMHC method achieves the state-of-the-art performance and is demonstrated to predict binding affinities to a series of MHC molecules with few binders accurately. These results have implications for understanding receptor-ligand interactions involved in MHC-peptide binding.

scholarly journals H-2M molecules, like MHC class II molecules, are targeted to parasitophorous vacuoles of Leishmania-infected macrophages and internalized by amastigotes of L. amazonensis and L. mexicana

1999 ◽  
Vol 112 (15) ◽  
pp. 2559-2570
Author(s):  
J.C. Antoine ◽  
T. Lang ◽  
E. Prina ◽  
N. Courret ◽  
R. Hellio
Keyword(s):  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Large Fraction ◽  
Peptide Binding ◽  
Leishmania Species ◽  
Class Ii ◽  
Antigenic Peptides ◽  
Mouse Macrophages ◽  
Peptide Binding Groove ◽  
Binding Groove

In their amastigote stage, Leishmania are obligatory intracellular parasites of mammalian macrophages, residing and multiplying within phagolysosomal compartments called parasitophorous vacuoles (PV). These organelles have properties similar to those described for the MHC class II compartments of antigen-presenting cells, sites where peptide-class II molecule complexes are formed before their expression at the cell surface. After infection with Leishmania amazonensis or L. mexicana, endocytosis and degradation of class II molecules by intracellular amastigotes have also been described, suggesting that these parasites have evolved mechanisms to escape the potentially hazardous antigen-presentation process. To determine whether these events extend to other molecules of the antigen-presentation machinery, we have now studied the fate of the MHC molecule H-2M in mouse macrophages infected with Leishmania amastigotes. At least for certain class II alleles, H-2M is an essential cofactor, which catalyses the release of the invariant chain-derived CLIP peptide from the peptide-binding groove of class II molecules and facilitates the binding of antigenic peptides. H-2M was detected in PV of mouse macrophages infected with various Leishmania species including L. amazonensis, L. mexicana, L. major and L. donovani. PV thus contain all the molecules required for the formation of peptide-class II molecule complexes and especially of complexes with parasite peptides. The present data indicate, however, that if this process occurs, it does not lead to a clear increase of SDS-stable compact (alpha)(beta) dimers of class II. In PV that contained L. amazonensis or L. mexicana, both class II and H-2M molecules often colocalized at the level where amastigotes bind to the PV membrane, suggesting that these molecules are physically associated, directly or indirectly, and possibly interact with parasite components. Furthermore, as class II molecules, H-2M molecules were internalized by amastigotes of these Leishmania species and reached parasite compartments that also contained class II molecules. Immunostaining of H-2M within parasites was increased by treatment of infected macrophages with the cysteine protease inhibitors Z-Phe-AlaCHN2 or Z-Phe-PheCHN2 or by incubation of the parasites with the same inhibitors before infection. These data thus support the idea that amastigotes of certain Leishmania species capture and degrade some of the molecules required for antigen presentation. To examine whether endocytosis of class II molecules by the parasites occurs through interactions with parasite components involving their peptide-binding groove, we made use of the fact that a large fraction of the class II molecules of H-2M(alpha) knock-out H-2(b) mice are occupied by the peptide CLIP and are unable to bind other peptides. We found that, in Leishmania-infected macrophages of these mutant mice, class II-CLIP complexes reached PV and were internalized by amastigotes. These results thus prove that endocytosis of class II molecules by amastigotes (1) is H-2M-independent and (2) does not necessarily involve the peptide-binding pocket of these molecules. Altogether, these data are compatible with an endocytic mechanism based on general properties shared by classical and non-classical class II molecules.

Inefficient Peptide Binding by Cell-Surface Class II MHC Molecules

1997 ◽  
Vol 182 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Melanie A. Sherman ◽  
Dominique A. Weber ◽  
Ellen A. Spotts ◽  
Joseph C. Moore ◽  
Peter E. Jensen
Keyword(s):  
Cell Surface ◽  
Peptide Binding ◽  
Class Ii ◽  
Mhc Molecules ◽  
Class Ii Mhc

scholarly journals Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility

2014 ◽  
Vol 111 (10) ◽  
pp. 3787-3792 ◽  
Author(s):  
Hui Jin ◽  
Noriko Arase ◽  
Kouyuki Hirayasu ◽  
Masako Kohyama ◽  
Tadahiro Suenaga ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Surface ◽  
Peptide Binding ◽  
Class Ii ◽  
Hla Class Ii ◽  
Hla Dr ◽  
Peptide Binding Groove ◽  
Binding Groove ◽  
Hla Class Ii Alleles ◽  
Arthritis Susceptibility

Specific HLA class II alleles are strongly associated with susceptibility to rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to RA has remained unclear. Recently, we found a unique function of HLA class II molecules: their ability to aberrantly transport cellular misfolded proteins to the cell surface without processing to peptides. Rheumatoid factor (RF) is an autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected in 70–80% of RA patients but also in patients with other diseases. Here, we report that intact IgG heavy chain (IgGH) is transported to the cell surface by HLA class II via association with the peptide-binding groove and that IgGH/HLA class II complexes are specifically recognized by autoantibodies in RF-positive sera from RA patients. In contrast, autoantibodies in RF-positive sera from non-RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for that allele’s association with RA was observed (r = 0.81; P = 4.6 × 10−5). Our findings suggest that IgGH complexed with certain HLA class II alleles is a target for autoantibodies in RA, which might explain why these HLA class II alleles confer susceptibility to RA.

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