scholarly journals A Peptide-binding Motif for I-Ag7, the Class II Major Histocompatibility Complex (MHC) Molecule of NOD and Biozzi AB/H Mice

1997 ◽  
Vol 185 (6) ◽  
pp. 1013-1022 ◽  
Author(s):  
Leonard C. Harrison ◽  
Margo C. Honeyman ◽  
Sylvie Trembleau ◽  
Silvia Gregori ◽  
Fabio Gallazzi ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Critical Role ◽  
Peptide Binding ◽  
Class Ii ◽  
Binding Motif ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Hla Dq

The class II major histocompatibility complex molecule I-Ag7 is strongly linked to the development of spontaneous insulin-dependent diabetes mellitus (IDDM) in non obese diabetic mice and to the induction of experimental allergic encephalomyelitis in Biozzi AB/H mice. Structurally, it resembles the HLA-DQ molecules associated with human IDDM, in having a non-Asp residue at position 57 in its β chain. To identify the requirements for peptide binding to I-Ag7 and thereby potentially pathogenic T cell epitopes, we analyzed a known I-Ag7-restricted T cell epitope, hen egg white lysozyme (HEL) amino acids 9–27. NH2- and COOH-terminal truncations demonstrated that the minimal epitope for activation of the T cell hybridoma 2D12.1 was M12-R21 and the minimum sequence for direct binding to purified I-Ag7 M12-Y20/ K13-R21. Alanine (A) scanning revealed two primary anchors for binding at relative positions (p) 6 (L) and 9 (Y) in the HEL epitope. The critical role of both anchors was demonstrated by incorporating L and Y in poly(A) backbones at the same relative positions as in the HEL epitope. Well-tolerated, weakly tolerated, and nontolerated residues were identified by analyzing the binding of peptides containing multiple substitutions at individual positions. Optimally, p6 was a large, hydrophobic residue (L, I, V, M), whereas p9 was aromatic and hydrophobic (Y or F) or positively charged (K, R). Specific residues were not tolerated at these and some other positions. A motif for binding to I-Ag7 deduced from analysis of the model HEL epitope was present in 27/30 (90%) of peptides reported to be I-Ag7–restricted T cell epitopes or eluted from I-Ag7. Scanning a set of overlapping peptides encompassing human proinsulin revealed the motif in 6/6 good binders (sensitivity = 100%) and 4/13 weak or non-binders (specificity = 70%). This motif should facilitate identification of autoantigenic epitopes relevant to the pathogenesis and immunotherapy of IDDM.

scholarly journals Bordetella pertussis Proteins Dominating the Major Histocompatibility Complex Class II-Presented Epitope Repertoire in Human Monocyte-Derived Dendritic Cells

2014 ◽  
Vol 21 (5) ◽  
pp. 641-650 ◽  
Author(s):  
Rachel M. Stenger ◽  
Hugo D. Meiring ◽  
Betsy Kuipers ◽  
Martien Poelen ◽  
Jacqueline A. M. van Gaans-van den Brink ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Bordetella Pertussis ◽  
Human Monocyte ◽  
Class Ii ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Content Type ◽  
Histocompatibility Complex

ABSTRACTKnowledge of naturally processedBordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presentedB. pertussisCD4+T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4+T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the naturalB. pertussisepitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition ofB. pertussis. A more complete understanding of hallmarks inB. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies.

scholarly journals Syk Tyrosine Kinase and B Cell Antigen Receptor (BCR) Immunoglobulin-α Subunit Determine BCR-mediated Major Histocompatibility Complex Class II–restricted Antigen Presentation

1998 ◽  
Vol 188 (5) ◽  
pp. 819-831 ◽  
Author(s):  
Danielle Lankar ◽  
Volker Briken ◽  
Kristin Adler ◽  
Peter Weiser ◽  
Sylvanie Cassard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Α Subunit ◽  
Histocompatibility Complex

Stimulation of CD4+ helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-α/Ig-β heterodimers which, second, target antigens to MHC class II–containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-α–associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-α cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide– MHC class II complexes through antigen targeting by BCR subunits.

scholarly journals Precise prediction of major histocompatibility complex class II-peptide interaction based on peptide side chain scanning.

1994 ◽  
Vol 180 (6) ◽  
pp. 2353-2358 ◽  
Author(s):  
J Hammer ◽  
E Bono ◽  
F Gallazzi ◽  
C Belunis ◽  
Z Nagy ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Peptide Binding ◽  
Class Ii ◽  
Side Chain ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Precise Prediction ◽  
Binding Peptides ◽  
Peptide Interaction

We describe here a new method for predicting class II major histocompatibility complex-binding peptides, based on the preferences observed in a systematic series of peptide binding experiments where each position in a "minimal" peptide was replaced individually by every amino acid. The DRB1*0401 peptide binding preferences were determined and incorporated into a computer program that looks through sequences for potential epitopes and assigns each a score. These scores correlate well with previously determined T cell epitopes of foreign antigens and endogenous peptides from self proteins. Our findings hold implications for the design of subunit vaccines and in the identification of autoantigenic peptide regions within self proteins.

Immuno-informatics-based identification of novel potential B cell and T cell epitopes to fight Zika virus infections

2020 ◽  
Vol 20 ◽  
Author(s):  
Wahiba Ezzemani ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Jalal Nourlil ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
B Cell ◽  
Zika Virus ◽  
T Cell Epitopes ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Virus Infections ◽  
Histocompatibility Complex

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.

scholarly journals Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression.

1993 ◽  
Vol 177 (6) ◽  
pp. 1699-1712 ◽  
Author(s):  
E K Bikoff ◽  
L Y Huang ◽  
V Episkopou ◽  
J van Meerwijk ◽  
R N Germain ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Critical Role ◽  
Class Ii ◽  
Intact Protein ◽  
Invariant Chain ◽  
Major Histocompatibility ◽  
Protein Antigens ◽  
Histocompatibility Complex ◽  
Class Ii Alpha

We used gene targeting techniques to produce mice lacking the invariant chain associated with major histocompatibility complex (MHC) class II molecules. Cells from these mice show a dramatic reduction in surface class II, resulting from both defective association of class II alpha and beta chains and markedly decreased post-Golgi transport. The few class II alpha/beta heterodimers reaching the cell surface behave as if empty or occupied by an easily displaced peptide, and display a distinct structure. Mutant spleen cells are defective in their ability to present intact protein antigens, but stimulate enhanced responses in the presence of peptides. These mutant mice have greatly reduced numbers of thymic and peripheral CD4+ T cells. Overall, this striking phenotype establishes that the invariant chain plays a critical role in regulating MHC class II expression and function in the intact animal.

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