scholarly journals MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy

2016 ◽  
Vol 28 (5) ◽  
pp. 1651-1664 ◽  
Author(s):  
Zhao Cui ◽  
Li-jun Xie ◽  
Fang-jin Chen ◽  
Zhi-yong Pei ◽  
Li-jie Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mhc Class Ii ◽  
Membranous Nephropathy ◽  
Class Ii ◽  
Idiopathic Membranous Nephropathy ◽  
Amino Acid Residues ◽  
Risk Alleles

scholarly journals The MHC class II-associated invariant chain contains two endosomal targeting signals within its cytoplasmic tail

1993 ◽  
Vol 106 (3) ◽  
pp. 831-846 ◽  
Author(s):  
J. Pieters ◽  
O. Bakke ◽  
B. Dobberstein
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Mhc Class Ii ◽  
Cytoplasmic Tail ◽  
Class Ii ◽  
Endocytic Pathway ◽  
Invariant Chain ◽  
Amino Acid Residues ◽  
Marker Proteins ◽  
Membrane Spanning

The oligomeric complex formed by major histocompatibility complex (MHC) class II alpha and beta chains and invariant chain (Ii) assembles in the endoplasmic reticulum and is then transported via the Golgi complex to compartments of the endocytic pathway. When Ii alone is expressed in CV1 cells it is sorted to endosomes. The Ii cytoplasmic tail has been found to be essential for targeting to these compartments. In order to characterize further the signals responsible for endosomal targeting, we have deleted various segments of the cytoplasmic tail. The Ii mutants were transiently expressed and the cellular location of the proteins was analyzed biochemically and morphologically. The cytoplasmic tail of Ii was found to contain two endosomal targeting sequences within its cytoplasmic tail; one targeting sequence was present within amino acid residues 12–29 and deletion of this segment revealed the presence of a second endosomal targeting sequence, located within the first 11 amino acid residues. The presence of a leucine-isoleucine pair at positions 7 and 8 within this sequence was found to be essential for endosomal targeting. In addition, the presence of this L-I motif lead to accumulation of Ii molecules in large endosomal vacuoles containing lysosomal marker proteins. Both wild type Ii and Ii mutant molecules containing only one endosomal targeting sequence were rapidly internalized from the plasma membrane. When the Ii cytoplasmic tail was fused to the membrane-spanning region of neuraminidase, a resident plasma membrane protein, the resulting chimera (INA) was found in endocytic compartments containing lysosomal marker proteins. Thus the cytoplasmic tail of Ii is sufficient for targeting to the endocytic/lysosomal pathway.

Involvement of class II β-chain amino acid residues 85 and 86 in T-cell allorecognition

1990 ◽  
Vol 27 (3) ◽  
pp. 240-253 ◽  
Author(s):  
David D. Eckels ◽  
Mary J. Geiger ◽  
Thomas W. Sell ◽  
Jack A. Gorski
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Class Ii ◽  
Amino Acid Residues ◽  
Β Chain

scholarly journals Conformation of MHC class II I-Ag7 is sensitive to the P9 anchor amino acid in bound peptide

2007 ◽  
Vol 19 (9) ◽  
pp. 1103-1113 ◽  
Author(s):  
A. Gardiner ◽  
K. A. Richards ◽  
A. J. Sant ◽  
L. S. Arneson
Keyword(s):  
Amino Acid ◽  
Mhc Class Ii ◽  
Class Ii

HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy

2018 ◽  
Vol 94 (5) ◽  
pp. 974-982 ◽  
Author(s):  
Huai-yu Wang ◽  
Zhao Cui ◽  
Li-jun Xie ◽  
Li-jie Zhang ◽  
Zhi-Yong Pei ◽  
...  
Keyword(s):  
Amino Acid ◽  
Membranous Nephropathy ◽  
Clinical Phenotype ◽  
Class Ii ◽  
Hla Class Ii ◽  
Single Amino Acid ◽  
Hla Class Ii Alleles

scholarly journals Correlation of structure with T cell responses of the three members of the HLA-DRw52 allelic series.

1989 ◽  
Vol 170 (3) ◽  
pp. 1027-1032 ◽  
Author(s):  
J Gorski ◽  
C Irle ◽  
E M Mickelson ◽  
M J Sheehy ◽  
A Termijtelen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Theoretical Model ◽  
T Cell ◽  
Gene Conversion ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Allelic Series ◽  
T Cell Clones ◽  
Cell Responses ◽  
Cell Clones

A third allele at the DRB3 locus, DRw52c, represents an intermediate sequence between DRw52a and DRw52b and may have arisen by a gene conversion-like event. The recognition of cells bearing these molecules by a number of alloreactive and antigen-specific DR-restricted T cell clones was analyzed. On the basis of a theoretical model of HLA class II structure, distinct amino acid clusters have been identified as motifs controlling TCR recognition. These are located both in the cleft and in the alpha-helical edge of the MHC class II recognition platform. Motifs shared between two alleles may restrict public T cell clones.

Potential Immunogenicity of Amino Acid Sequences Encoded by Ns-SNPs in Factor VIII,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3329-3329 ◽  
Author(s):  
Devi Gunasekera ◽  
Ruth A. Ettinger ◽  
Richard J. Hughes ◽  
Melinda S. Epstein ◽  
John C. Barrett ◽  
...  
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Binding Assays ◽  
Helper T Cell ◽  
Strong Affinity ◽  
Sequence Variations ◽  
T Cell Stimulation

Abstract Abstract 3329 Development of inhibitory antibodies that block factor VIII (FVIII) pro-coagulant function requires T-cell help. In order for T-cell stimulation to occur, one or more FVIII-derived peptides must first bind effectively to MHC Class II (e.g. HLA-DRB1) receptors on the surface of antigen presenting cells. If this Class II-peptide complex is recognized by a receptor on a helper T cell, then high-avidity Class II-peptide-T-cell receptor interactions can (but may not) cause proliferation and cytokine secretion leading to anti-FVIII antibody production. Thus the initial binding of a FVIII peptide to a Class II receptor can initiate an HLA-restricted cascade of events that leads to inhibitor formation in hemophilia A (HA) patients. Non-hemophilic, non-synonymous single nucleotide polymorphisms (ns-SNPs) in the human F8 gene were identified previously (Viel et al., Blood 109:3713–24, 2007) that result in the FVIII sequence variations R484H, R776G, D1241E and M2238V. Recombinant FVIII proteins with R484, R776, either D1241 or E1241, and M2238 are currently used therapeutically. The potential immunogenicity of FVIII peptides corresponding to these sequence variations is now being analyzed directly using in vitro assays employing cellular fractions of HA blood, recombinant proteins and synthetic peptides. These studies are motivated by a concern that some HA patients who express even very low levels of their endogenous, hemophilic FVIII, which should tend to promote immune tolerance to exogenous FVIII, could in principle develop inhibitors provoked solely by amino acid sequence mismatch(es) at sites in FVIII encoded by ns-SNPs. This could happen in patients with specific HLA types if their corresponding Class II receptors presented a FVIII peptide that then stimulated a helper T-cell response. Synthetic FVIII peptides containing both alternate sequences encoded by these 4 ns-SNPs were tested for binding to the monomeric extracellular domains of 10 common DRB1 alleles using competitive binding assays. The results are as follows: (1) 484: R484 peptides had strong affinity (IC50 < 1 mM) for DRB1*15:01 and DRB1*03:01; H484 peptides had moderate affinity (IC50 = 1–10 mM) for DRB1*03:01 and DRB1*15:01; both R484 and H484 peptides bound with moderate affinity to DRB1*11:04 and DRB1*04:04; (2) 776: R776 and G776 peptides had moderate affinity for DRB1*09:01; (3) 1241: E1241 peptides had strong affinity for DRB1*09:01 and moderate affinity for DRB1*01:01, D1241 peptides bound weakly (IC50 = 30–50 mM) to DRB1*09:01 and DRB1*01:01; (4) 2238: Both M2238 and V2238 peptides had strong affinity for DRB1*03:01 and moderate affinity binding to DRB1*01:01, DRB1*11:04, DRB1*11:01 and DRB1*04:04. Results of the binding assays compared reasonably well with computer-predicted affinities of the peptides for some of the better-characterized HLA-DRB1 alleles. T-cell stimulation and MHC Class II tetramer staining experiments (which can unambiguously identify antigen-specific T cells) were next carried out using CD4 T cells from (1) 4 HA subjects (1 with a current inhibitor, 1 with a previous inhibitor and 2 without inhibitors) whose F8 gene encoded the V2238 variant and therefore had been treated with a therapeutic FVIII produce that was mismatched at this site with respect to the endogenous sequence encoded by their hemophilic F8 gene; and (2) from 4 HA subjects with the M2238 variant. All 8 patients expressed either the DRB1*03:01 or DRB1*11:01 alleles (one expressed both). No peptides corresponding to regions encoded by either version of this ns-SNP were recognized as T-cell epitopes by CD4 cells from these subjects, despite moderate to strong binding affinity of the peptides for DR0301 and DR1101 proteins. This suggests that the immunogenicity of these FVIII regions in HA patients who express these F8 and HLA genotype combinations may be less than might have been anticipated based on the binding data. HA patients with HLA-DRB1 receptors that do not effectively bind peptides encoded by ns-SNPs in the F8 gene would be expected to have a low risk of developing helper T-cell responses to FVIII sequences encoded by these ns-SNPs. Thus, the negative as well as positive peptide-binding assay results have significant clinical and pharmaceutical relevance. Results of assays such as those described above could be useful in developing improved methods to assess the relative risk of individual HA patients developing an inhibitor. Disclosures: Pratt: Bayer, CSL Behring, Pfizer: Research Funding; Puget Sound Blood Center: Patents & Royalties.

Molecular characterization of MHC class II DRA cDNA in Deoni cattle

2018 ◽  
Author(s):  
K. Swathi ◽  
M. Gnana Prakash ◽  
D. Sakaram ◽  
T. Raghunandan ◽  
A. Sarat Chandra ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Mhc Class Ii ◽  
Signal Peptide ◽  
Class Ii ◽  
Glycosylation Site ◽  
Amino Acid Sequences ◽  
Conserved Residues ◽  
A2 Domain

The present study was undertaken to clone and characterize DRA gene in Deoni cattle. The cDNA for the DRA gene was amplified by using specific primers designed based on available cattle sequences and purified products were cloned in competent E.coli (DH5á) strain. The full length 1013bp product of cDNA of DRA contained a single ORF of 762 nucleotides that coded for 253 amino acids translated product. Twenty four amino acids formed signal peptide while 229 constituted mature peptide. The deduced amino acid sequences resembled those of class II molecules of other species for all the conserved residues having critical functional role. But a single N-linked glycosylation site in á1 was observed in cattle and buffalo when compared to human and swine which contain a second site in á2 domain. The signal peptide was found more variable among the species compared. Comparison of nucleotide and amino acid sequences among related species and dendrogram constructed revealed that the cattle sequences are more similar to buffalo sequences.

scholarly journals Risk alleles for IgA nephropathy-associated SNPs conferred completely opposite effects to idiopathic membranous nephropathy in Chinese Han

2017 ◽  
Vol 65 (5) ◽  
pp. 1059-1064 ◽  
Author(s):  
Xiaosong Qin ◽  
Chen Wang ◽  
Guanting Lu ◽  
Mengle Peng ◽  
Guixue Cheng ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Membranous Nephropathy ◽  
Idiopathic Membranous Nephropathy ◽  
Chinese Han ◽  
Risk Alleles
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