Bacterial antigens elicit T cell responses via adaptive and transitional immune recognition

2001 ◽  
Vol 4 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Brad T Cookson ◽  
Lisa A Cummings ◽  
Sara L Rassoulian Barrett
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Immune Recognition ◽  
Cell Responses ◽  
Bacterial Antigens

scholarly journals 2729. mRNA Vaccines Encoding Conserved Influenza Antigens Induce Robust and Durable Immunity in Rhesus Macaques

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S961-S961
Author(s):  
Jessica Flynn ◽  
Kara Cox ◽  
Sinoeun Touch ◽  
Yangsi Ou ◽  
Teresa Weber ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Rhesus Macaques ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Immune Recognition ◽  
Serum Antibodies ◽  
Ifn Gamma ◽  
Cell Responses ◽  
Lipid Nanoparticle

Abstract Background In response to immune pressure, influenza virus evolves, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response that can recognize multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the immunogenicity of mRNA vaccines encoding the stem domain of hemagglutinin (HA) or nucleoprotein (NP) in nonhuman primates (NHPs). Methods Rhesus macaques were immunized three times intramuscularly, at 28 day intervals, with lipid nanoparticle-encapsulated mRNA encoding either HA stem (Yassine et al, 2015) or NP. Serum and PBMCs were collected up to 14 or 24 weeks, respectively, after the last vaccination. The magnitude and durability of humoral and cell-mediated immunity were evaluated. ELISA, competition ELISA, an in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter bioassay, and microneutralization assays were used to characterize serum immune responses. Intracellular cytokine staining (IFN-gamma and IL-2) was used to assess antigen-specific T-cell responses. Results HA stem-immunized NHPs developed a robust anti-stem binding titer after a single vaccine dose, and after two doses, serum antibodies recognized several antigenically distinct Group 1 HA proteins. This broad antibody response persisted for at least 14 weeks post-dose 3 (PD3). Serum antibodies showed ADCC activity and competed with a well-characterized broadly neutralizing antibody, CR9114, for binding to HA stem; however, the polyclonal serum had only minimal activity against a panel of H1N1 viruses in a microneutralization assay. HA-specific CD4+ T-cell responses were detectable PD3. A robust antibody binding response was also detected in NP-vaccinated NHPs, and titers remained high for at least 14 weeks PD3. Additionally, these animals developed robust NP-specific T-cell responses that persisted for at least 24 weeks PD3. On average, 0.5% of CD4+ and 4% of CD8+ T cells produced IFN-gamma in response to NP peptide stimulation at the peak of the response, 2 weeks after the last vaccine dose was administered. Conclusion Lipid nanoparticle-encapsulated mRNA vaccines encoding conserved influenza antigens induce a robust and durable immune response in NHPs. Disclosures All authors: No reported disclosures.

scholarly journals Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Aránzazu Cruz-Adalia ◽  
Guillermo Ramirez-Santiago ◽  
Jesús Osuna-Pérez ◽  
Mónica Torres-Torresano ◽  
Virgina Zorita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Bacterial Antigens ◽  
Memory Cd8 T Cell

scholarly journals Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells

2011 ◽  
Vol 208 (10) ◽  
pp. 2005-2016 ◽  
Author(s):  
Mercedes B. Fuertes ◽  
Aalok K. Kacha ◽  
Justin Kline ◽  
Seng-Ryong Woo ◽  
David M. Kranz ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Innate Immune ◽  
Tumor Control ◽  
Type I ◽  
Immune Recognition ◽  
Cell Responses ◽  
Host Type ◽  
T Cell Priming

Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c+ cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α+ dendritic cells, which were demonstrated to be essential using Batf3−/− mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α+ DCs.

scholarly journals Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities

2004 ◽  
Vol 78 (5) ◽  
pp. 2187-2200 ◽  
Author(s):  
Nicole Frahm ◽  
B. T. Korber ◽  
C. M. Adams ◽  
J. J. Szinger ◽  
R. Draenert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Peptide Sequence ◽  
Immune Recognition ◽  
Cell Responses ◽  
Clade B ◽  
Immunodeficiency Virus

ABSTRACT Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8+-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8+-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8+-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations.

scholarly journals IMMU-07. A PHASE I STUDY OF MULTIPLE PEPTIDE TUMOR-ASSOCIATED ANTIGEN VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv6-iv6
Author(s):  
Kristen Batich ◽  
Gary Archer ◽  
Pamela Norberg ◽  
David Ashley ◽  
John Sampson ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Malignant Glioma ◽  
T Cell Responses ◽  
Class Ii ◽  
Immune Recognition ◽  
Newly Diagnosed ◽  
Peptide Vaccination ◽  
Who Grade ◽  
Cell Responses

Abstract INTRODUCTION Targeting tumor-associated antigens (TAAs) via peptide vaccination has been tested against malignant glioma with minimal success. Poor responses are attributed to relatively low antigen level expression of the TAA and insufficient CD8+ T cell responses. Including a universal class II epitope that provides CD4+ T cell help towards CD8+ responses has been tested with the immunogenic tetanus toxoid epitope P30, but P30 has been employed as a separate peptide in this regard. The current study will employ targeting of three major glioma TAAs: EphA2, pp65 from Cytomegalovirus, and survivin. The ability to induce more potent TAA-specific immune responses will be tested using two novel strategies: P30-linked TAA peptides and a combinatorial vaccination of the linked peptides (P30-EPS). HYPOTHESES In Evaluation of Tumor Associated P30-Peptide Antigen I (ETAPA-I), P30-EPS is anticipated to have an acceptable toxicity profile. Multi-peptide vaccination is thought to bypass tumor heterogeneity and selection of antigen-negative clones, known as antigen escape. Moreover, the administration of EPS covalently linked to P30 is anticipated to increase the magnitude of antigen-specific immune responses and elicit both CD4- and CD8-mediated immune recognition. TRIAL DESIGN/OBJECTIVES A maximum of 24 patients with newly diagnosed, unmethylated WHO grade IV glioma will be treated. Following resection and standard of care chemoradiation, patients will be vaccinated serially during the priming phase (Day 1-22) and booster phase (Day 84 and 140). All P30-EPS vaccines during priming and boosting phases are co-administered with the adjuvant Hiltonol (Oncovir, poly-ICLC), and patients self-administer Hiltonol throughout the booster phase. The primary endpoint will evaluate the safety profile of P30-EPS. Secondary objectives include polyfunctional T-cell responses specific to EphA2, pp65 and survivin, TCR diversity, and survival. CONCLUSION We describe a study that employs known TAA targets of malignant glioma with the novel strategy of combinatorial class II-linked peptide vaccination.

scholarly journals Author Correction: Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Aránzazu Cruz-Adalia ◽  
Guillermo Ramirez-Santiago ◽  
Jesús Osuna-Pérez ◽  
Mónica Torres-Torresano ◽  
Virgina Zorita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Bacterial Antigens ◽  
Memory Cd8 T Cell

scholarly journals Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+T Cells

2016 ◽  
Vol 90 (19) ◽  
pp. 8552-8562 ◽  
Author(s):  
Esther Jimenez-Moyano ◽  
Alba Ruiz ◽  
Henrik N. Kløverpris ◽  
Maria T. Rodriguez-Plata ◽  
Ruth Peña ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cellular Immunity ◽  
Acute Infection ◽  
Cyclophilin A ◽  
T Cell Responses ◽  
Immune Recognition ◽  
Cell Responses ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTTripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type 1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two nonhuman TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+T cells. We illustrate how TRIM5 restriction improves CD8+T-cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the nonimmunosuppressive analog of cyclosporine (CsA), sarcosine-3(4-methylbenzoate)–CsA (SmBz-CsA), we found a significant reduction in CD107a/MIP-1β expression in HIV-1-specific CD8+T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for nonhuman TRIM5 variants in cellular immunity. We hypothesize that TRIM5 can couple innate viral sensing and CD8+T-cell activation to increase species barriers against retrovirus infection.IMPORTANCENew therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The nonhuman TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+T-cell-mediated inhibition through the direct activation of HIV-1-specific CD8+T-cell responses. We found that the potency in CD8+activation was stronger for RhT5 variants and capsid-specific CD8+T cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection.

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