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Major Histocompatibility Complex Antigens

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1. A unique major histocompatibility complex Class II-binding register correlates with HLA-DR11-associated immunogenicity of the major K blood group antigen. (Abstract)

A unique major histocompatibility complex Class II-binding register correlates with HLA-DR11-associated immunogenicity of the major K blood group antigen. Kell is a glycoprotein expressed on red blood cells (RBCs). Its K and k variants contain either Met (K antigen) or Thr (k antigen) at Position 193, respectively. Development of anti-K after K-mismatched antigen exposure via blood transfusions or pregnancy can destroy RBCs, leading to hemolytic transfusion reactions and hemolytic disease (...) of the fetus and newborn. The immunogenicity of overlapping 15-mer Kell peptides with M193 or T193 at every possible position was investigated previously. Interestingly, Peptide W179 to M193, with the polymorphic M193T residue at the peptide's C-terminus, was the most effective at stimulating CD4 T cells from a series of K-immunized women.This study investigates the basis for HLA restriction of anti-K immune responses. Major histocompatibility complex Class II (MHCII)-binding prediction algorithms

2018 Transfusion

2. Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE<sup>-/-</sup> Mice. Full Text available with Trip Pro

Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE-/- Mice. Hypercholesterolemic mice lacking factors required for activation of CD4+ T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on major (...) histocompatibility complex class II (MHCII) leads to activation of proatherogenic Th1 cells. In this study, we wanted to determine the role of antigen presentation on MHCII in atherosclerosis development.Apolipoprotein E (ApoE-/-) mice deficient for MHCII (ApoE-/-MHCII-/-) were used to study the role of MHCII in atherosclerosis development.Compared with ApoE-/- mice, ApoE-/-MHCII-/- mice had reduced levels of CD4+ T cells, immunoglobulin G and M levels, and Th1 and Th2 cytokines in plasma. CD8+ T cells were

2019 Circulation

3. Programmed self-assembly of peptide–major histocompatibility complex for antigen-specific immune modulation Full Text available with Trip Pro

Programmed self-assembly of peptide–major histocompatibility complex for antigen-specific immune modulation A technology to prime desired populations of T cells in the body-particularly those that possess low avidity against target antigen-would pave the way for the design of new types of vaccination for intractable infectious diseases or cancer. Here, we report such a technology based on positive feedback-driven, programmed self-assembly of peptide-major histocompatibility complex (pMHC (...) a mechanical force that stabilizes interactions at the TCR-pMHC interface and facilitates repeated, serial pMHC encounters. Furthermore, ANXA5 quickly arranges into uniform 2D matrices, thereby prompting TCR cross-linking. Fusion of ANXA5 to pMHC augments lymphocyte activation by several orders of magnitude (>1,000-fold), bypasses the need for costimulation, and breaks tolerance against a model self-antigen in vivo. Our study opens the door to the application of synthetic, feedback-driven self-assembly

2018 Proceedings of the National Academy of Sciences of the United States of America

4. Quantification of HLA-DM-Dependent Major Histocompatibility Complex of Class II Immunopeptidomes by the Peptide Landscape Antigenic Epitope Alignment Utility Full Text available with Trip Pro

Quantification of HLA-DM-Dependent Major Histocompatibility Complex of Class II Immunopeptidomes by the Peptide Landscape Antigenic Epitope Alignment Utility The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers (...) epitopes from antigenic peptides of variable lengths. Here, we present the design and benchmarking of a new algorithm [peptide landscape antigenic epitope alignment utility (PLAtEAU)] allowing the identification and label-free quantification (LFQ) of shared consensus epitopes arising from series of nested peptides. The algorithm simplifies the complexity of the dataset while allowing the identification of nested peptides within relatively short segments of protein sequences. Moreover, we apply

2018 Frontiers in immunology

5. Human Macrophages Escape Inhibition of Major Histocompatibility Complex-Dependent Antigen Presentation by Cytomegalovirus and Drive Proliferation and Activation of Memory CD4+ and CD8+ T Cells Full Text available with Trip Pro

Human Macrophages Escape Inhibition of Major Histocompatibility Complex-Dependent Antigen Presentation by Cytomegalovirus and Drive Proliferation and Activation of Memory CD4+ and CD8+ T Cells Human cytomegalovirus (HCMV) persistently infects 40-90% of the human population but in the face of a normal immune system, viral spread and dissemination are efficiently controlled thus preventing clinically signs and disease. HCMV-infected hosts produce a remarkably large amount of HCMV-specific CD4 (...) + and CD8+ T cells that can even reach 20-50% of total T memory cells in the elderly. How HCMV may elicit such large and long-lasting T-cell responses in the absence of detectable viremia has not been elucidated yet. Additionally, HCMV is known to encode several gene products that potently inhibit T-cell recognition of infected cells. The best characterized are the four immune evasive US2, US3, US6, and US11 genes that by different mechanisms account for major histocompatibility complex (MHC) class I

2018 Frontiers in immunology

6. Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides Full Text available with Trip Pro

Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9 (...) epitopes and the further development of the AIDS vaccine.IMPORTANCE Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp167 blocks the left side of pocket A, causing P1D

2018 Journal of virology

7. Immune privilege disruption in folliculotropic mycosis fungoides: investigation of major histocompatibility complex antigen expression. (Abstract)

Immune privilege disruption in folliculotropic mycosis fungoides: investigation of major histocompatibility complex antigen expression. Folliculotropic mycosis fungoides (FMF) is a cutaneous T-cell lymphoma mainly affecting the hair follicle, which seems to represent a place of immune privilege phenomenon.To explore a possible role of immune privilege (IP) in FMF analyzing the major histocompatibility complex (MHC) expression.Immunohistochemistry for HLA-G and MHC-II was performed to formalin

2018 International Journal of Dermatology

8. Genetic Diversity of Bovine Major Histocompatibility Complex Class II DRB3 locus in cattle breeds from Asia compared to those from Africa and America Full Text available with Trip Pro

Genetic Diversity of Bovine Major Histocompatibility Complex Class II DRB3 locus in cattle breeds from Asia compared to those from Africa and America Genetic polymorphisms and diversity of BoLA-DRB3.2 are essential because of DRB3 gene's function in innate immunity and its association with infectious diseases resistance or tolerance in cattle. The present study was aimed at assessing the level of genetic diversity of DRB3 in the exon 2 (BoLA-DRB3.2) region in African, American and Asian cattle (...) analyses revealed a non-significant higher rate of non-synonymous (dN) compared to synonymous substitutions (dS). The ratio of dN/dS substitution across the breeds were observed to be greater than one suggesting that variation at the antigen-binding sites is under positive selection; thus increasing the chances of these breeds to respond to wide array of pathogenic attacks. An analysis of molecular variance revealed that 94.01 and 5.99% of the genetic variation was attributable to differences within

2018 Journal of genomics

9. Treatment of Patients With Metastatic Cancer Using a Major Histocompatibility Complex Class II-Restricted T-Cell Receptor Targeting the Cancer Germline Antigen MAGE-A3. Full Text available with Trip Pro

Treatment of Patients With Metastatic Cancer Using a Major Histocompatibility Complex Class II-Restricted T-Cell Receptor Targeting the Cancer Germline Antigen MAGE-A3. Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I-restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8+ T cells or bulk T (...) cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4+ T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3). Patients and Methods Patients received a lymphodepleting preparative regimen, followed by adoptive transfer of purified CD4+ T cells, retrovirally transduced with MAGE-A3 TCR plus systemic high-dose IL-2. A cell dose escalation was conducted, starting

2017 Journal of Clinical Oncology

10. Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control Full Text available with Trip Pro

Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens (...) this commonality, polymorphic amino acid differences between allotypes alter the ability of MHC I molecules to change shape (that is, their conformational plasticity). We discuss how the peptide loading co-factor tapasin might modify this plasticity to augment peptide loading. Lastly, we consider recent findings concerning the functions of the non-classical MHC I molecule HLA-E as well as the tapasin-related protein TAPBPR (transporter associated with antigen presentation binding protein-related), which has

2017 F1000Research

11. Genetic defects of the IRF1-mediated major histocompatibility complex class I antigen presentation pathway occur prevalently in the JAK2 gene in non-small cell lung cancer Full Text available with Trip Pro

Genetic defects of the IRF1-mediated major histocompatibility complex class I antigen presentation pathway occur prevalently in the JAK2 gene in non-small cell lung cancer Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ (...) in loss of IFNγ-induced IRF1 and cell surface HLA-ABC in JAK2 wildtype NSCLC cells, whereas expression of exogenous JAK2 in H1573 cells restored the IFNγ responses. These findings show that JAK2 deficiency is the major mechanism of genetic defects of the IFNγ-IRF1 pathway in NSCLC and reveal a previously unrecognized significance of chromosome 9p deletion in NSCLC.

2017 Oncotarget

12. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation Full Text available with Trip Pro

Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation Antigen presentation by major histocompatibility complex (MHC) proteins is essential for adaptive immunity. Prior to presentation, peptides need to be generated from proteins that are either produced by the cell's own translational machinery or that are funneled into the endo-lysosomal vesicular system. The prolonged interaction between a T cell receptor and specific pMHC (...) complexes, after an extensive search process in secondary lymphatic organs, eventually triggers T cells to proliferate and to mount a specific cellular immune response. Once processed, the peptide repertoire presented by MHC proteins largely depends on structural features of the binding groove of each particular MHC allelic variant. Additionally, two peptide editors-tapasin for class I and HLA-DM for class II-contribute to the shaping of the presented peptidome by favoring the binding of high-affinity

2017 Frontiers in immunology

13. Impact of human sepsis on CCCTC-binding factor associated monocyte transcriptional response of Major Histocompatibility Complex II components. Full Text available with Trip Pro

Impact of human sepsis on CCCTC-binding factor associated monocyte transcriptional response of Major Histocompatibility Complex II components. Antigen presentation on monocyte surface to T-cells by Major Histocompatibility Complex, Class II (MHC-II) molecules is fundamental for pathogen recognition and efficient host response. Accordingly, loss of Major Histocompatibility Complex, Class II, DR (HLA-DR) surface expression indicates impaired monocyte functionality in patients suffering from (...) sepsis-induced immunosuppression. Besides the impact of Class II Major Histocompatibility Complex Transactivator (CIITA) on MHC-II gene expression, X box-like (XL) sequences have been proposed as further regulatory elements. These elements are bound by the DNA-binding protein CCCTC-Binding Factor (CTCF), a superordinate modulator of gene transcription. Here, we hypothesized a differential interaction of CTCF with the MHC-II locus contributing to an altered monocyte response in immunocompromised

2018 PLoS ONE

14. Major Histocompatibility Complex Antigens

Major Histocompatibility Complex Antigens Major Histocompatibility Complex Antigens Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 (...) Major Histocompatibility Complex Antigens Major Histocompatibility Complex Antigens Aka: Major Histocompatibility Complex Antigens , Human Leukocyte Antigen B27 , HLA-B27 II. Indications Limited use in clinical practice May be indicated if strongly suspected III. Labs: Methods of Testing binding to patient's cells Mixed responses against specific targets Hybridization to DNA probes IV. Efficacy for : 84% for : 96% V. Causes: Positive HLA-B27 (with Incidence) : 95% ( ): 80% (Spondylitis with ): 70

2018 FP Notebook

15. A Multiprotein Complex Consisting of the Cellular Coactivator p300, AP-1/ATF, as well as NF-κB IS Responsible for the Activation of the Mouse Major Histocompatibility Class I (H-2Kb) Enhancer A Full Text available with Trip Pro

A Multiprotein Complex Consisting of the Cellular Coactivator p300, AP-1/ATF, as well as NF-κB IS Responsible for the Activation of the Mouse Major Histocompatibility Class I (H-2Kb) Enhancer A Major histocompatibility complex (MHC) class I genes encode highly polymorphic antigens that play an essential role in a number of immunological processes. Their expression is activated in response to a variety of signals and is mediated through several promoter elements among which the enhancer (...) element is bound by at least two distinct heterodimers of the AP-1/ATF transcription factor family, namely c-Jun/ATF-2 and c-Jun/Fra2. Moreover, our data reveal that the enhancer A is simultaneously bound by AP-1/ATF and rel/NF-kappaB transcription factors and that the cellular coactivator p300, which enhances enhancer A-driven reporter gene expression if cotransfected, is recruited to the enhancer A through this multiprotein complex. In contrast to the complete enhancer A, neither the EnA-TRE nor

2018 Gene expression

16. Determination of a Predictive Cleavage Motif for Eluted Major Histocompatibility Complex Class II Ligands Full Text available with Trip Pro

Determination of a Predictive Cleavage Motif for Eluted Major Histocompatibility Complex Class II Ligands CD4+ T cells have a major role in regulating immune responses. They are activated by recognition of peptides mostly generated from exogenous antigens through the major histocompatibility complex (MHC) class II pathway. Identification of epitopes is important and computational prediction of epitopes is used widely to save time and resources. Although there are algorithms to predict binding (...) affinity of peptides to MHC II molecules, no accurate methods exist to predict which ligands are generated as a result of natural antigen processing. We utilized a dataset of around 14,000 naturally processed ligands identified by mass spectrometry of peptides eluted from MHC class II expressing cells to investigate the existence of sequence signatures potentially related to the cleavage mechanisms that liberate the presented peptides from their source antigens. This analysis revealed preferred amino

2018 Frontiers in immunology

17. Both Major Histocompatibility Complex Class I (MHC-I) and MHC-II Molecules Are Required, while MHC-I Appears To Play a Critical Role in Host Defense against Primary Coxiella burnetii Infection Full Text available with Trip Pro

Both Major Histocompatibility Complex Class I (MHC-I) and MHC-II Molecules Are Required, while MHC-I Appears To Play a Critical Role in Host Defense against Primary Coxiella burnetii Infection To understand the role of class I major histocompatibility complex (MHC-I) and class II MHC (MHC-II) antigen presentation pathways in host defense against Coxiella burnetii infection, we examined whether MHC-I or MHC-II deficiency in mice would significantly influence their susceptibility to virulent C (...) cells appear to play a more critical role in controlling bacterial replication. Additionally, although NMI infection induced more severe disease in TAP1-deficient mice than in their WT counterparts, TAP1 deficiency in mice did not significantly influence their ability to eliminate C. burnetii This suggests that C. burnetii antigen presentation to CD8+ T cells by the MHC-I classical pathway may depend only partially on TAP1. Furthermore, granzyme B deficiency in mice did not significantly alter

2018 Infection and immunity

18. T Cell Receptor–Major Histocompatibility Complex Interaction Strength Defines Trafficking and CD103+ Memory Status of CD8 T Cells in the Brain Full Text available with Trip Pro

T Cell Receptor–Major Histocompatibility Complex Interaction Strength Defines Trafficking and CD103+ Memory Status of CD8 T Cells in the Brain T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells (...) in the chronically Toxoplasma gondii-infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7. The three TN CD8 T cell clones span a wide range of affinities to MHCI-ROP7. These three CD8 T cell clones have a distinct and fixed hierarchy in terms of effector function in response to the antigen measured as proliferation capacity, trafficking, T cell maintenance

2018 Frontiers in immunology

19. Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients Full Text available with Trip Pro

Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients Evidence of antibody-mediated injury in the absence of donor-specific HLA antibodies (HLA-DSA) has recently emerged, suggesting a role of antibodies in targeting non-HLA antigens expressed on renal allograft tissue. However, the clinical significance of pre-transplant non-HLA antibodies remains unclear. We compared

2018 Annals of laboratory medicine

20. Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma. Full Text available with Trip Pro

Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma. Purpose Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/ CD274(PD-L1)/ PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (...) (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial. Methods HRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components-β2-microglobulin, MHC class I, and MHC class II-by immunohistochemistry

2018 Journal of Clinical Oncology

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