479 results match your criteria crossreactive cell

Functional characterization of CD4+ T cell receptors crossreactive for SARS-CoV-2 and endemic coronaviruses.

J Clin Invest 2021 05;131(10)

Bloomberg~Kimmel Institute for Cancer Immunotherapy.

BACKGROUNDRecent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2.METHODSWe used the viral functional expansion of specific T cells (ViraFEST) platform to identify T cell responses crossreactive for the spike (S) glycoproteins of SARS-CoV-2 and CCCs at the T cell receptor (TCR) clonotype level in convalescent COVID-19 patients (CCPs) and SARS-CoV-2-unexposed donors. Read More

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Monoclonal antibody against H1N1 influenza virus hemagglutinin cross reacts with hnRNPA1 and hnRNPA2/B1.

Mol Med Rep 2020 Nov 7;22(5):3969-3975. Epub 2020 Sep 7.

Central Laboratory of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Medical School, Xi'an Jiaotong University, Shaanxi Province Research Centre of Cell Immunological Engineering and Technology, Key Laboratory of Microbial Infections and Autoimmune Diseases, Xi'an, Shaanxi 710068, P.R. China.

Following influenza A vaccination, certain individuals exhibit adverse reactions in the nervous system, which causes a problem with the safety of the influenza A vaccine. However, to the best of our knowledge, the underlying mechanism of this is unknown. The present study revealed that a monoclonal antibody (H1‑84mAb) against the H1N1 influenza virus hemagglutinin (HA) protein cross‑reacted with an antigen from brain tissue. Read More

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November 2020

Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis.

J Clin Med 2020 Jun 29;9(7). Epub 2020 Jun 29.

Euro-Mediterranean Institute of Science and Technology (IEMEST), 90141 Palermo, Italy.

Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host's antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. Read More

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Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance.

Hum Vaccin Immunother 2020 6;16(2):251-268. Epub 2019 Dec 6.

Department of Immunology, VLP Biotech, Inc., JLABS San Diego, San Diego, CA, USA.

An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4/CD8 T cell response, poor cytokine production, insufficient neutralizing antibody (nAb) and poor response to HBsAg vaccination characterize CHB infection. Read More

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Human thioredoxin, a damage-associated molecular pattern and Malassezia-crossreactive autoallergen, modulates immune responses via the C-type lectin receptors Dectin-1 and Dectin-2.

Sci Rep 2019 08 1;9(1):11210. Epub 2019 Aug 1.

Hannover Medical School, Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover, Germany.

Human thioredoxin (hTrx), which can be secreted from cells upon stress, functions in allergic skin inflammation as a T cell antigen due to homology and cross-reactivity with the fungal allergen Mala s13 of the skin-colonizing yeast Malassezia sympodialis. Recent studies have shown that cell wall polysaccharides of Malassezia are detected by the immune system via the C-type lectin receptors Dectin-1 and Dectin-2, which are expressed on myeloid cells. Therefore, this study aimed to investigate a putative interaction between Dectin-1, Dectin-2 and the allergens Mala s13 and hTrx. Read More

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Fungus Among Us: The Frenemies Within.

Trends Immunol 2019 06 30;40(6):469-471. Epub 2019 Apr 30.

University of Pittsburgh, Department of Medicine, Division of Rheumatology and Clinical Immunology, Pittsburgh, PA 15261, USA. Electronic address:

A recent study shows that the commensal fungus Candida albicans is an inducer of differentiation of human CD4 Th17 cells that harbor heterologous specificity for other fungi, which may explain evolutionary benefits of C. albicans as a commensal microbe (Bacher et al. Cell 2019;176;1340-1355). Read More

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Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire.

J Clin Invest 2019 03 28;129(6):2446-2462. Epub 2019 Mar 28.

Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, Columbia University, New York, New York, USA.

We investigated human T-cell repertoire formation using high throughput TCRβ CDR3 sequencing in immunodeficient mice receiving human hematopoietic stem cells (HSCs) and human thymus grafts. Replicate humanized mice generated diverse and highly divergent repertoires. Repertoire narrowing and increased CDR3β sharing was observed during thymocyte selection. Read More

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Amino Acid Substitutions N123D and N149D in Hemagglutinin Molecule Enhance Immunigenicity of Live Attenuated Influenza H7N9 Vaccine Strain in Experiment.

Bull Exp Biol Med 2019 Mar 22;166(5):631-636. Epub 2019 Mar 22.

A. A. Smorodintsev Department of Virology, Institute of Experimental Medicine, St. Petersburg, Russia.

We compared three cold-adapted live attenuated influenza vaccine strains prepared by reverse genetics methods on the basis of master donor virus A/Leningrad/134/17/57 and influenza H7N9 strains A/Anhui/1/2013 and A/Shanghai/1/2013. Two strains based on A/Anhui/1/2013 differed by amino acid positions 123 and 149 in HA1 (123N/149N; 123D/149D). All strains efficiently replicated in developing chicken embryos; A/Shanghai/1/2013-based strain and A/Anhui/1/2013-123N/149N variant were characterized by reduced replication in MDCK cells. Read More

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Anti-HLA Antibody: The Role of Epitopes in Organ Transplantation.

Hassan Argani

Exp Clin Transplant 2019 01;17(Suppl 1):38-42

From the Transplantation Ward, Modarres Hospital, Shahidbeheshti University of Medical Sciences, Tehran, Iran.

Recent developments have been achieved for better matching in solid-organ transplantation by epitope matching. HLA matching remains a standard immunologic strategy to determine organ compatibility for recipients. Advancements in tissue typing have introduced HLA matching at the epitope level. Read More

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January 2019

Directed evolution of broadly crossreactive chemokine-blocking antibodies efficacious in arthritis.

Nat Commun 2018 04 13;9(1):1461. Epub 2018 Apr 13.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, 02139, USA.

Chemokine receptors typically have multiple ligands. Consequently, treatment with a blocking antibody against a single chemokine is expected to be insufficient for efficacy. Here we show single-chain antibodies can be engineered for broad crossreactivity toward multiple human and mouse proinflammatory ELR CXC chemokines. Read More

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A modified HLA-A*0201-restricted CTL epitope from human oncoprotein (hPEBP4) induces more efficient antitumor responses.

Cell Mol Immunol 2018 08 29;15(8):768-781. Epub 2018 Jan 29.

National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.

We previously identified human phosphatidylethanolamine-binding protein 4 (hPEBP4) as an antiapoptotic protein with increased expression levels in breast, ovarian and prostate cancer cells, but low expression levels in normal tissues, which makes hPEBP4 an attractive target for immunotherapy. Here, we developed hPEBP4-derived immunogenic peptides for inducing antigen-specific cytotoxic T lymphocytes (CTLs) targeting breast cancer. A panel of hPEBP4-derived peptides predicted by peptide-MHC-binding algorithms was evaluated to characterize their HLA-A2. Read More

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Identification and characterization of epitopes from influenza A virus hemagglutinin that induce broadly cross-reactive antibodies.

Int J Mol Med 2018 Mar 22;41(3):1673-1682. Epub 2017 Dec 22.

Central Experimental Laboratory, Shaanxi Provincial People's Hospital, Key Laboratory of Infection and Immunity of Shaanxi Province, Xi'an, Shaanxi 710068, P.R. China.

Influenza is the most common infectious disease and is caused by influenza A virus (IAV) infection. Hemagglutinin (HA) is an important viral protein of influenza A and is a major component of current IAV vaccines. The side effects associated with IAV vaccination are well studied; however, the HA‑induced immunopathological changes have remained largely elusive. Read More

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Uncommon structural motifs dominate the antigen binding site in human autoantibodies reactive with basement membrane collagen.

Mol Immunol 2016 08 20;76:123-33. Epub 2016 Jul 20.

Department of Medicine, Duke University Medical Center, Durham, N.C., USA; Durham VA Medical Center, Durham, N.C., USA. Electronic address:

Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human CD34+ hematopoietic stem cells and immunized with the non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen. This antigen is expressed in lungs and kidneys and is targeted by autoantibodies in anti-glomerular basement membrane (GBM) nephritis and Goodpasture syndrome (GPS), prototypic human organ-specific autoimmune diseases. Read More

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Crossreactive αβ T Cell Receptors Are the Predominant Targets of Thymocyte Negative Selection.

Immunity 2015 Nov 27;43(5):859-69. Epub 2015 Oct 27.

Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address:

The precise impact of thymic positive and negative selection on the T cell receptor (TCR) repertoire remains controversial. Here, we used unbiased, high-throughput cloning and retroviral expression of individual pre-selection TCRs to provide a direct assessment of these processes at the clonal level in vivo. We found that 15% of random TCRs induced signaling and directed positive (7. Read More

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November 2015

Immunization with Ty21a live oral typhoid vaccine elicits crossreactive multifunctional CD8+ T-cell responses against Salmonella enterica serovar Typhi, S. Paratyphi A, and S. Paratyphi B in humans.

Mucosal Immunol 2015 Nov 15;8(6):1349-59. Epub 2015 Apr 15.

Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Previously we have extensively characterized Salmonella enterica serovar Typhi (S. Typhi)-specific cell-mediated immune (CMI) responses in volunteers orally immunized with the licensed Ty21a typhoid vaccine. In this study we measured Salmonella-specific multifunctional (MF) CD8+ T-cell responses to further investigate whether Ty21a elicits crossreactive CMI against S. Read More

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November 2015

Vaccination and heterologous immunity: educating the immune system.

Trans R Soc Trop Med Hyg 2015 Jan;109(1):62-9

Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605, USA

This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. Read More

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January 2015

Functional aspects of intrahepatic hepatitis B virus-specific T cells induced by therapeutic DNA vaccination.

Mol Ther 2015 Mar 10;23(3):578-90. Epub 2014 Dec 10.

Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Current therapies for the hepatitis B virus (HBV), a major cause of severe liver disease, suppress viral replication but replication rebounds if therapy is withdrawn. It is widely accepted that immune activation is needed to control replication off-therapy. To specifically activate T cells crossreactive between the hepatitis B core and e antigens (HBcAg/HBeAg) in chronically infected patients, we developed a therapeutic vaccine candidate. Read More

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Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice.

J Transl Med 2014 Jul 25;12:207. Epub 2014 Jul 25.

Department of Immunology, Centre for Immune Regulation, University of Oslo, Oslo University Hospital, Rikshospitalet, NO-0424 Oslo, Norway.

Background: Therapeutic idiotypic (Id) vaccination is an experimental treatment for selected B cell malignancies. A broader use of Id-based vaccination, however, is hampered by the complexity and costs due to the individualized production of protein vaccines. These limitations may be overcome by targeted DNA vaccines encoding stereotyped immunoglobulin V regions of B cell malignancies. Read More

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Rho GTPase Rac1: molecular switch within the galectin network and for N-glycan α2,6-sialylation/O-glycan core 1 sialylation in colon cancer in vitro.

Folia Biol (Praha) 2014 ;60(3):95-107

Ludwig-Maximilians-University Munich, Faculty of Veterinary Medicine, Institute of Physiological Chemistry, Munich, Germany.

The Rho GTPase Rac1 is a multifunctional protein working through different effector pathways. The emerging physiological significance of glycanlectin recognition gives reason to testing the possibility for an influence of modulation of Rac1 expression on these molecular aspects. Using human colon adenocarcinoma (SW620) cells genetically engineered for its up- and down-regulation (Rac1+ and Rac1- cells) along with wild-type and mock-transfected control cells, the questions are addressed whether the presence of adhesion/growth-regulatory galectins and distinct aspects of cell surface glycosylation are affected. Read More

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T cell mediated immunity to influenza: mechanisms of viral control.

Trends Immunol 2014 Aug 16;35(8):396-402. Epub 2014 Jul 16.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia. Electronic address:

Infection with influenza A virus (IAV) is a major cause of worldwide morbidity and mortality. Recent findings indicate that T cell immunity is key to limiting severity of disease arising from IAV infection, particularly in instances where antibody immunity is ineffective. As such, there is a need to understand better the mechanisms that mediate effective IAV-specific cellular immunity, especially given that T cell immunity must form an integral part of any vaccine designed to elicit crossreactive immunity against existing and new strains of influenza virus. Read More

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Ongoing activation of autoantigen-specific B cells in primary biliary cirrhosis.

Hepatology 2014 Nov 29;60(5):1708-16. Epub 2014 Sep 29.

Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA.

Unlabelled: The serologic hallmark of primary biliary cirrhosis (PBC), the antimitochondrial response to the E2 component of the pyruvate dehydrogenase complex (PDC-E2), has unique features, including continuous high titers of immunoglobulin M (IgM) and IgG reactivity throughout all stages of disease, capable not only of target enzyme inhibition, but also crossreactive with chemical xenobiotics that share molecular homology with the inner lipoyl domain of PDC-E2; such chemicals have been proposed as potential etiological agents. We used flow cytometry and enzyme-linked immunospot assay (ELISPOT) to examine B-cell subsets in 59 subjects, including 28 with PBC, 13 with primary sclerosing cholangitis (PSC), and 18 healthy controls. Strikingly, in PBC, although there were no significant differences in B-cell phenotype subpopulations, 10% of the total IgG and IgA plasmablast population and 23% of the IgM plasmablast population were uniquely reactive with PDC-E2, detected in the CXCR7+ CCR10low plasmablast population. Read More

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November 2014

On plasma cell longevity or brevity.

Rolf Zinkernagel

Expert Rev Vaccines 2014 Jul 7;13(7):821-3. Epub 2014 Jun 7.

Department of Pathology, University Hospital Zürich, Schmelzbergstrasse 12, 8091 Zürich, Switzerland.

The seemingly long half-life of antibody-producing plasma cells demonstrated by antigen-binding (ELISA type of) assays as compared with the short-livedness of neutralizing and protective antibody-producing plasma cells is explained here by the heterogeneity and multiple crossreactive antibodies detected by ELISA-type assays. While DNP-specific B cell frequencies are about 10(-2) that of virus, serotype-specific B cell frequencies are about 10(-5)-10(-6). Therefore, the seemingly long-lived multiple low-affinity crossreactive antibody-producing plasma cells represent a collective of little if any biological or evolutionary relevance. Read More

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Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy.

Nat Rev Cancer 2014 Feb;14(2):135-46

1] de Duve Institute and the Université catholique de Louvain, B-1200 Brussels, Belgium. [2] Ludwig Institute for Cancer Research, B-1200 Brussels, Belgium.

In this Timeline, we describe the characteristics of tumour antigens that are recognized by spontaneous T cell responses in cancer patients and the paths that led to their identification. We explain on what genetic basis most, but not all, of these antigens are tumour specific: that is, present on tumour cells but not on normal cells. We also discuss how strategies that target these tumour-specific antigens can lead either to tumour-specific or to crossreactive T cell responses, which is an issue that has important safety implications in immunotherapy. Read More

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February 2014

Characterization of T-cell responses to cryptic epitopes in recipients of a noncodon-optimized HIV-1 vaccine.

J Acquir Immune Defic Syndr 2014 Feb;65(2):142-50

*Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL; †Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA; and ‡Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL.

Introduction: Cryptic epitopes (CEs) can be encoded by any of the 5 alternative reading frames (ARFs, 2 sense and 3 antisense) of a known gene. Although CE responses are commonly detected during HIV-1 infection, it is not known whether these responses are induced after vaccination.

Methods: Using a bioinformatic approach, we determined that vaccines with codon-optimized HIV inserts significantly skewed CE sequences and are not likely to induce crossreactive responses to natural HIV CE. Read More

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February 2014

Cellular immune correlates of protection against symptomatic pandemic influenza.

Nat Med 2013 Oct 22;19(10):1305-12. Epub 2013 Sep 22.

Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, UK.

The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether crossreactive cellular immunity limits symptomatic illness in antibody-naive individuals. We followed 342 healthy adults through the UK pandemic waves and correlated the responses of pre-existing T cells to the pH1N1 virus and conserved core protein epitopes with clinical outcomes after incident pH1N1 infection. Read More

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October 2013

[Local antibody immune responses in influenza patients and persons vaccinated with seasonal, pre-pandemic, and pandemic live attenuated influenza vaccines].

Vopr Virusol 2013 May-Jun;58(3):37-42

Mucosal immunity is one of the most important factors of human anti-influenza defense. The data about local immune responses in influenza A (H3N2) patients and in persons vaccinated within 2000-2009 with different seasonal LAIVs, A (H1N1)pdm2009 LAIV, and A (H5N2) LAIV are discussed. The influenza infection resulted in the larger quantities of local IgA and IgG conversions than seasonal LAIV vaccination. Read More

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September 2013

Outer membrane protein A (OmpA) from Shigella flexneri 2a: a promising subunit vaccine candidate.

Vaccine 2013 Aug 10;31(36):3644-50. Epub 2013 Jun 10.

Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, Kolkata 700010, West Bengal, India.

Shigellosis is the leading cause of childhood mortality and morbidity. Despite many years of extensive research a practical vaccine is not yet available against the disease. Recent studies illustrate that bacterial outer membrane proteins are budding target as vaccine antigen. Read More

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The fibrin-derived citrullinated peptide β60-74Cit₆₀,₇₂,₇₄ bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies.

Ann Rheum Dis 2014 Jun 1;73(6):1246-52. Epub 2013 May 1.

, Epidermis Differentiation and Rheumatoid Autoimmunity' Laboratory, UMR CNRS 5165, INSERM U 1056, Toulouse III University, , Toulouse, France.

Objectives: To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36-50Cit₃₈,₄₂ and/or β60-74Cit₆₀,₇₂,₇₄, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies.

Methods: 617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36-50Cit₃₈,₄₂, anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies, and by nephelometry for rheumatoid factor (RF). Read More

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Inflammation and atherosclerosis: direct versus indirect mechanisms.

Curr Opin Pharmacol 2013 Apr 26;13(2):154-60. Epub 2013 Jan 26.

Department of Pathology, University of Washington, USA.

It is now widely accepted that the development of atherosclerotic lesions involves a chronic inflammatory response that includes both innate and adaptive immune mechanisms. However, it is still unclear precisely what induces the inflammatory response. Furthermore, inflammation within the blood vessel can be divided into direct mechanisms where the primary inflammatory events occur within the intima of the blood vessel and contribute to both the initiation and progression of the plaques and indirect mechanisms where inflammation at nonvascular sites can contribute to the progression of the lesions. Read More

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Development of measles virus-based shielded oncolytic vectors: suitability of other paramyxovirus glycoproteins.

Cancer Gene Ther 2013 Feb 11;20(2):109-16. Epub 2013 Jan 11.

Department of Molecular Medicine, Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Antibody-mediated neutralization may interfere with the efficacy of measles virus (MV) oncolysis. To circumvent vector neutralization, we sought to exchange the envelope glycoproteins, hemagglutinin (H) and fusion (F), with those from the non-crossreactive Tupaia paramyxovirus (TPMV). To sustain efficient particle assembly, we generated hybrid glycoproteins with the MV cytoplasmic tails and the TPMV ectodomains. Read More

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February 2013