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 Characterization of a renal tubular epithelial cell line which secretes the autologous target antigen of autoimmune experimental interstitial nephritis.

1988 ◽  
Vol 107 (4) ◽  
pp. 1359-1368 ◽  
Author(s):  
T P Haverty ◽  
C J Kelly ◽  
W H Hines ◽  
P S Amenta ◽  
M Watanabe ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Cell Surface ◽  
Interstitial Nephritis ◽  
Class Ii ◽  
Target Antigen ◽  
Mhc Molecules ◽  
Epithelial Growth Factor ◽  
Class Ii Mhc ◽  
Epithelial Growth

Proximal tubular epithelial cells from mice which develop autoimmune interstitial nephritis were found to express the nephritogenic target antigen, 3M-1. Anti-3M-1 mAbs (alpha 3M-1-Ab) were used to positively select for 3M-1-secreting tubular epithelium and, after stabilization in culture, this new cell line (MCT) was examined for the production of several moieties important to either immune interactions or to the development of extracellular matrix. Alkaline phosphatase-staining MCT cells also express epithelial growth factor receptors with a Kd of 0.87 nM and an epithelial growth factor receptor constant (Ro) of 2.1 X 10(4) receptors/cell. MCT culture supernatants contain greater amounts of laminin, and types IV and V procollagens compared to types I and III procollagens, and growing MCT cells on type I collagen matrix causes them to preferentially secrete even more type IV and V procollagen. The 30,000-Mr 3M-1 antigen could be immunoprecipitated from biosynthetically labeled MCT cell supernatants with alpha 3M-1-Ab. An identical-sized moiety was isolated by immunoaffinity chromatography from collagenase-solubilized mouse kidney tubular basement membranes. The 3M-1 antigen can be found on the MCT cell surface by radioimmunoassay, or deposited in a linear array in the extracellular matrix surrounding the MCT cells in culture by immunofluorescence. Mature messenger RNA species for both class I and class II major histocompatibility complex (MHC) molecules were detected by Northern hybridization, and their corresponding cell surface gene products were detected by cytofluorography of MCT cells stained with haplotype-specific antibodies. Both the cell surface 3M-1 and the small amounts of detected class II MHC molecules appear to be biologically functional, as MCT cells can support the proliferation of 3M-1-specific, class II MHC-restricted helper T cells in culture. These findings suggest that MCT cells provide all the necessary biological parameters for interfacing both as the target of a nephritogenic immune response, and as a potential source for new extracellular matrix which develops as a fibrogenic response to interstitial nephritis.

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 Peptide Binding to Active Class II MHC Protein on the Cell Surface

2001 ◽  
Vol 166 (11) ◽  
pp. 6680-6685 ◽  
Author(s):  
Judith F. Vacchino ◽  
Harden M. McConnell
Keyword(s):  
Cell Surface ◽  
Peptide Binding ◽  
Class Ii ◽  
Class Ii Mhc ◽  
Active Class

Electron microscopy analysis of degenerating pancreatic ß cells in transgenic mice expressing the MHC Class I antigen Dd

1990 ◽  
Vol 48 (3) ◽  
pp. 548-549
Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Disease Process ◽  
Class Ii ◽  
Class I ◽  
Type I ◽  
Aberrant Expression ◽  
Mhc Molecules ◽  
Endogenous Insulin ◽  
Class Ii Mhc ◽  
Ifn Γ

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.

MHC Sınıf I ve MHC Sınıf II Gen Düzenlenmesi

2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Gene Regulation ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Regulation Mechanisms

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription

scholarly journals HLA-DQB1 codon 57 is critical for peptide binding and recognition.

1996 ◽  
Vol 183 (3) ◽  
pp. 1253-1258 ◽  
Author(s):  
W W Kwok ◽  
M E Domeier ◽  
M L Johnson ◽  
G T Nepom ◽  
D M Koelle
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Cell Clone ◽  
Peptide Binding ◽  
Class Ii ◽  
Binding Studies ◽  
Peptide Complex ◽  
Mhc Molecules ◽  
Hla Dq ◽  
T Cell Clone

The association of specific HLA-DQ alleles with autoimmunity is correlated with discrete polymorphisms in the HLA-DQ sequence that are localized within sites suitable for peptide recognition. The polymorphism at residue 57 of the DQB1 polypeptide is of particular interest since it may play a major structural role in the formation of a salt bridge structure at one end of the peptide-binding cleft of the DQ molecules. This polymorphism at residue 57 is a recurrent feature of HLA-DQ evolution, occurring in multiple distinct allelic families, which implies a functional selection for maintaining variation at this position in the class II molecule. We directly tested the amino acid polymorphism at this site as a determinant for peptide binding and for antigen-specific T cell stimulation. We found that a single Ala-->Asp amino acid 57 substitution in an HLA-DQ3.2 molecule regulated binding of an HSV-2 VP-16-derived peptide. A complementary single-residue substitution in the peptide abolished its binding to DQ3.2 and converted it to a peptide that can bind to DQ3.1 and DQ3.3 Asp-57-positive MHC molecules. These binding studies were paralleled by specific T cell recognition of the class II-peptide complex, in which the substituted peptide abolished T cell reactivity, which was directed to the DQ3.2-peptide complex, whereas the same T cell clone recognized the substituted peptide presented by DQ3.3, a class II restriction element differing from DQ3.2 only at residue 57. This structural and functional complementarity for residue 57 and a specific peptide residue identifies this interaction as a key controlling determinant of restricted recognition in HLA-DQ-specific immune response.

Phosphorylation of class I but not class II MHC molecules by membrane-localized protein kinase C

1989 ◽  
Vol 26 (12) ◽  
pp. 1095-1104 ◽  
Author(s):  
Teresa Burke ◽  
Karen Pollok ◽  
William Cushley ◽  
E. Charles Snow
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Kinase C ◽  
Class Ii Mhc

scholarly journals Citrullination only infrequently impacts peptide binding to HLA class II MHC

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0177140 ◽  
Author(s):  
John Sidney ◽  
Stephane Becart ◽  
Mimi Zhou ◽  
Karen Duffy ◽  
Mikaela Lindvall ◽  
...  
Keyword(s):  
Peptide Binding ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class Ii Mhc
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