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https://www.readbyqxmd.com/read/28430664/identification-of-a-novel-pd-l1-positive-solid-tumor-transplantable-in-hla-a-0201-drb1-0101-transgenic-mice
#1
Laurie Rangan, Jeanne Galaine, Romain Boidot, Mohamad Hamieh, Magalie Dosset, Julie Francoual, Laurent Beziaud, Jean-René Pallandre, Elodie Lauret Marie Joseph, Afag Asgarova, Christophe Borg, Talal Al Saati, Yann Godet, Jean Baptiste Latouche, Séverine Valmary-Degano, Olivier Adotévi
HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429374/immune-response-of-highly-conserved-influenza-a-virus-matrix-1-peptides
#2
Neha Lohia, Manoj Baranwal
Influenza vaccine development is considered to be complicated and challenging. Constantly evolving influenza viruses require continuous global monitoring and reformulation of the vaccine strains. Peptide conserved among different strains and subtypes of influenza A virus are well-thought-out to be attractive targets for development of cross protective influenza vaccine based on cellular response. Three highly conserved (> 90%) matrix 1 peptides ILGFVFTLTVPSERGLQRRRF (PM 1), LIRHENRMVLASTTAKA (PM 2) and LQAYQKRMGVQMQR (PM 3) containing multiple T cell epitopes have been assessed for their immunogenic potential in vitro, subjecting peripheral blood mononuclear cells from healthy volunteers to repetitive stimulation of these chemically synthesised peptides and measuring their interferon (IFN)-γ level and proliferation by ELISA (Enzyme-linked immunosorbent assay) and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide) assay, respectively...
April 21, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28429069/mupexi-prediction-of-neo-epitopes-from-tumor-sequencing-data
#3
Anne-Mette Bjerregaard, Morten Nielsen, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA binding and similarity to normal peptides...
April 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28425860/a-novel-recombinant-multi-epitope-vaccine-could-induce-specific-cytotoxic-t-lymphocyte-response-in-vitro-and-in-vivo
#4
Yahong Wu, Wenjie Zhai, Meng Sun, Zhe Zou, Xiuman Zhou, Guodong Li, Zhongyi Yan, Yuanming Qi, Yanfeng Gao
Cytotoxic T lymphocytes (CTLs) against various tumor antigens play an important role in elimination of tumor cells. To develop therapeutic vaccines that can induce specific immune response, we designed a novel recombinant multiepitope vaccine YL66 which consists of HLA-A2-restricted CTL epitopes from two widely expressed tumor antigen cyclooxygenase-2 and MAGE-4, linked with membrane permeable Tat-PTD and the universal T helper epitope. The DNA fragment of YL66 was cloned into pGEX-4T-2-YL66 and pcDNA3.1(+)-YL66, respectively...
April 19, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28423320/sequence-and-structural-analyses-reveal-distinct-and-highly-diverse-human-cd8-tcr-repertoires-to-immunodominant-viral-antigens
#5
Guobing Chen, Xinbo Yang, Annette Ko, Xiaoping Sun, Mingming Gao, Yongqing Zhang, Alvin Shi, Roy A Mariuzza, Nan-Ping Weng
A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8(+) TCR repertoires for two dominant viral epitopes: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL) of influenza A virus. The highly individualized repertoires (87-5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28421076/broad-based-cd4-t-cell-responses-to-influenza-a-virus-in-a-healthy-individual-who-lacks-typical-immunodominance-hierarchy
#6
Li Chen, Anjaleena Anthony, Sara Oveissi, Miaojuan Huang, Damien Zanker, Kun Xiao, Chao Wu, Quanming Zou, Weisan Chen
Influenza A virus (IAV) infection is a significant cause of morbidity and mortality worldwide. CD4(+) T cell responses have been shown to be important for influenza protection in mouse models and in human volunteers. IAV antigen-specific CD4(+) T cell responses were found to focus on matrix 1 (M1) and nucleoprotein (NP) at the protein antigen level. At the epitope level, only several epitopes within M1 and NP were recognized by CD4(+) T cells. And the epitope-specific CD4(+) T cell responses showed a typical immunodominance hierarchy in most of the healthy individuals studied...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28418077/therapeutic-protein-deimmunization-by-t-cell-epitope-removal-antigen-specific-immune-responses-in-vitro-and-in-vivo
#7
Saeme Asgari, Azadeh Ebrahim-Habibi, Mehdi Mahdavi, Mohammad Choopani, Hasan Mirzahoseini
Hirudin III is an effective anti-coagulant; however, in 40% of treated patients, a high-titer of anti-Hirudin III IgG antibodies is observed. Development of antibody responses requires the activation of helper T lymphocyte (HTL), which is dependent on peptide epitopes binding to HLA class II molecules. Based on computational prediction softwares, four new mutants of Hirudin III, T4K, S9G, V21G, and V21K, had been designed with the aim of reducing the binding affinity of these HTL epitopes. The constructed mutants have been purified and assayed for bioactivity...
April 18, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28414197/engineering-of-a-self-adjuvanted-itep-delivered-ctl-vaccine
#8
Shuyun Dong, Tiefeng Xu, Peng Wang, Peng Zhao, Mingnan Chen
Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in cancer and infectious disease therapy. We previously generated an immune-tolerant elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine and enhance the efficiency of the vaccine. To further optimize the vaccine carrier, we intended to potentiate its function by designing an iTEP-based carrier that was able to deliver adjuvant and a vaccine epitope as one molecule. Thus, we fused a 9-mer H100, a peptide derived from the high-mobility group box 1 protein (HMGB1) that could induce activation of dendritic cells (DCs), with an iTEP polymer to generate a new iTEP polymer named H100-iTEP...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28413500/enhancement-of-humoral-and-cell-mediated-immune-response-to-hpv16-l1-derived-peptides-subsequent-to-vaccination-with-prophylactic-bivalent-hpv-l1-virus-like-particle-vaccine-in-healthy-females
#9
Masato Yokomine, Satoko Matsueda, Kouichiro Kawano, Tetsuro Sasada, Akimasa Fukui, Takuto Yamashita, Nobukazu Komatsu, Shigeki Shichijo, Kazuto Tasaki, Ken Matsukuma, Kyogo Itoh, Toshiharu Kamura, Kimio Ushijima
Currently prophylactic HPV16/18 L1 virus-like particle (VLP) vaccines are employed with great success for the prevention of HPV infection. However, limited information is available regarding the immune responses against human papillomavirus (HPV) 16/18 L1 subsequent to HPV16/18 L1 VLP vaccination, primarily due to the lack of widely used assays for immune monitoring. The aim of the present study was to identify HPV16 L1-derived B and T cell epitopes for monitoring the immune responses after HPV16/18 L1 VLP vaccination in healthy females...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28411163/development-of-a-multi-epitope-peptide-vaccine-inducing-robust-t-cell-responses-against-brucellosis-using-immunoinformatics-based-approaches
#10
Mahdiye Saadi, Ahmad Karkhah, Hamid Reza Nouri
Current investigations have demonstrated that a multi-epitope peptide vaccine targeting multiple antigens could be considered as an ideal approach for prevention and treatment of brucellosis. According to the latest findings, the most effective immunogenic antigens of brucella to induce immune responses are included Omp31, BP26, BLS, DnaK and L7-L12. Therefore, in the present study, an in silico approach was used to design a novel multi-epitope vaccine to elicit a desirable immune response against brucellosis...
April 11, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28410427/tcr-stimulation-strength-is-inversely-associated-with-establishment-of-functional-brain-resident-memory-cd8-t-cells-during-persistent-viral-infection
#11
Saumya Maru, Ge Jin, Todd D Schell, Aron E Lukacher
Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410303/personalized-therapy-tumor-antigen-discovery-for-adoptive-cellular-therapy
#12
Cassian Yee, Gregory A Lizee
Adoptive cell therapy using endogenous T cells involves the ex vivo isolation and expansion of antigen-specific T cells from the peripheral blood and is uniquely suited for validating and translating antigen discovery. Endogenous T-cell therapy does not require accessible tumor as a source of infiltrating T cells and is free of regulatory and logistical constraints associated with engineering T cells. Candidate epitope peptides identified through antigen discovery may be rapidly implemented as targets in clinical trials of endogenous T-cell therapy and even incorporated as an "ad hoc" approach to personalized treatment when autologous tumor is available...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410302/tumor-infiltrating-lymphocyte-therapy-and-neoantigens
#13
Paul F Robbins
The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410297/identification-of-immunogenic-epitopes-by-ms-ms
#14
Moreno Di Marco, Janet Kerstin Peper, Hans-Georg Rammensee
The interrogation of cell surface-presented immunogenic epitopes is of great importance to differentiate diseased cells in consequence to malignant transformation or viral infections. On the basis of this knowledge, next-generation immunotherapies against cancers, autoimmunity, or infectious diseases can be developed. The identification of altered peptide repertoires of transformed cells renders mass spectrometry-based analysis indispensable. This is evident considering the low correlation of gene or protein expression alterations, respectively, with changes in the peptide repertoire rendering those analyses less informative...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28407485/defective-hiv-1-proviruses-are-expressed-and-can-be-recognized-by-cytotoxic-t-lymphocytes-which-shape-the-proviral-landscape
#15
Ross A Pollack, R Brad Jones, Mihaela Pertea, Katherine M Bruner, Alyssa R Martin, Allison S Thomas, Adam A Capoferri, Subul A Beg, Szu-Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C Yong, Colin Kovacs, Erika Benko, Robert F Siliciano, Ya-Chi Ho
Despite antiretroviral therapy, HIV-1 persists in memory CD4(+) T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28404636/antibody-distance-from-the-cell-membrane-regulates-antibody-effector-mechanisms
#16
Kirstie L S Cleary, H T Claude Chan, Sonja James, Martin J Glennie, Mark S Cragg
Immunotherapy using mAbs, such as rituximab, is an established means of treating hematological malignancies. Abs can elicit a number of mechanisms to delete target cells, including complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, and Ab-dependent cellular phagocytosis. The inherent properties of the target molecule help to define which of these mechanisms are more important for efficacy. However, it is often unclear why mAb binding to different epitopes within the same target elicits different levels of therapeutic activity...
April 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28402260/dna-plasmid-vaccine-carrying-chlamydia-trachomatis-ct-major-outer-membrane-and-human-papillomavirus-16l2-proteins-for-anti-ct-infection
#17
Ledan Wang, Yiqi Cai, Yirong Xiong, Wangqi Du, Danwei Cen, Chanqiong Zhang, Yiling Song, Shanli Zhu, Xiangyang Xue, Lifang Zhang
Chlamydia trachomatis (Ct) is one of the most frequently encountered sexual infection all over the world, yielding tremendous reproductive problems (e.g. infertility and ectopic pregnancy) in the women. This work described the design of a plasmid vaccine that protect mice from Ct infection, and reduce productive tract damage by generating effective antibody and cytotoxic T cell immunity. The vaccine, s was composed of MOMP multi-epitope and HPV16L2 genes carried in pcDNA plasmid (i.e. pcDNA3.1/MOMP/HPV16L)...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401156/computational-identification-and-characterization-of-a-promiscuous-t-cell-epitope-on-the-extracellular-protein-85b-of-mycobacterium-spp-for-peptide-based-subunit-vaccine-design
#18
Md Saddam Hossain, Abul Kalam Azad, Parveen Afroz Chowdhury, Mamoru Wakayama
Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins of Mycobacterium spp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28400082/immune-dysregulation-in-immunodeficiency-disorders-the-role-of-t-cell-receptor-sequencing
#19
REVIEW
Gabriel K Wong, James M Heather, Sara Barmettler, Mark Cobbold
Immune dysregulation is a prominent feature of primary immunodeficiency disorders, which commonly manifested as autoimmunity, cytopenias and inflammatory bowel disease. In partial T-cell immunodeficiency disorders, it has been proposed that the imbalance between effector and regulatory T-cells drives the breakdown of peripheral tolerance. While there is no robust test for immune dysregulation, the T-cell receptor repertoire is used as a surrogate marker, and has been shown to be perturbed in a number of immunodeficiency disorders featuring immune dysregulation including Omenn's Syndrome, Wiskott-Aldrich Syndrome, and common variable immunodeficiency...
April 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28394921/cd8-t-cell-evasion-mandates-cd4-t-cell-control-of-chronic-gamma-herpesvirus-infection
#20
Cindy S E Tan, Clara Lawler, Philip G Stevenson
Gamma-herpesvirus infections are regulated by both CD4+ and CD8+ T cells. However clinical disease occurs mainly in CD4+ T cell-deficient hosts. In CD4+ T cell-deficient mice, CD8+ T cells control acute but not chronic lung infection by Murid Herpesvirus-4 (MuHV-4). We show that acute and chronic lung infections differ in distribution: most acute infection was epithelial, whereas most chronic infection was in myeloid cells. CD8+ T cells controlled epithelial infection, but CD4+ T cells and IFNγ were required to control myeloid cell infection...
April 2017: PLoS Pathogens
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