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Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers

Holland, Christopher J. ; Rizkallah, Pierre J. ; Vollers, Sabrina ; [et al.]

Springer Science and Business Media LLC ; 2012

In: Scientific Reports Vol. 2, No. 1 ( 2012-09-04)

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In: Scientific Reports, Springer Science and Business Media LLC, Vol. 2, No. 1 ( 2012-09-04)

Abstract: Successful immunity requires that a limited pool of αβ T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by ‘self’ major histocompatibility complex (pMHC) molecules. Structures of unligated and ligated MHC class-I-restricted TCRs with different ligands, supplemented with biophysical analyses, have revealed a number of important mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the influenza hemagglutinin antigen (HA 306–318 ) presented by HLA-DR1 or HLA-DR4 represents an ideal system for interrogating pMHC-II antigen recognition. Accordingly, we solved the structure of the unligated HA1.7 TCR and compared it to both complex structures. Despite a relatively rigid binding mode, HA1.7 T-cells could tolerate mutations in key contact residues within the peptide epitope. Thermodynamic analysis revealed that limited plasticity and extreme favorable entropy underpinned the ability of the HA1.7 T-cell clone to cross-react with HA 306–318 presented by multiple MHC-II alleles.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/srep00629

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2012

detail.hit.zdb_id: 2615211-3

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Safety and Enhanced Immunogenicity of a Hepatitis B Core Particle Plasmodium falciparum Malaria Vaccine Formulated in Adjuvant Montanide ISA 720 in a Phase I Trial

Oliveira, Giane A. ; Wetzel, Kristiane ; Calvo-Calle, J. Mauricio ; [et al.]

American Society for Microbiology ; 2005

In: Infection and Immunity Vol. 73, No. 6 ( 2005-06), p. 3587-3597

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In: Infection and Immunity, American Society for Microbiology, Vol. 73, No. 6 ( 2005-06), p. 3587-3597

Abstract: Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum -specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4 + T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate.

Type of Medium: Online Resource

ISSN: 0019-9567 , 1098-5522

URL: Article

DOI: 10.1128/IAI.73.6.3587-3597.2005

RVK:

XA 10000

Language: English

Publisher: American Society for Microbiology

Publication Date: 2005

detail.hit.zdb_id: 1483247-1

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An Unstable Th Epitope of P. falciparum Fosters Central Memory T Cells and Anti-CS Antibody Responses

Parra-López, Carlos A. ; Bernal-Estévez, David ; Vargas, Luis Eduardo ; [et al.]

Public Library of Science (PLoS) ; 2014

In: PLoS ONE Vol. 9, No. 7 ( 2014-7-1), p. e100639-

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In: PLoS ONE, Public Library of Science (PLoS), Vol. 9, No. 7 ( 2014-7-1), p. e100639-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0100639

DOI: 10.1371/journal.pone.0100639.g001

DOI: 10.1371/journal.pone.0100639.g002

DOI: 10.1371/journal.pone.0100639.g003

DOI: 10.1371/journal.pone.0100639.g004

DOI: 10.1371/journal.pone.0100639.g005

DOI: 10.1371/journal.pone.0100639.g006

DOI: 10.1371/journal.pone.0100639.g007

DOI: 10.1371/journal.pone.0100639.g008

DOI: 10.1371/journal.pone.0100639.t001

DOI: 10.1371/journal.pone.0100639.t002

DOI: 10.1371/journal.pone.0100639.t003

DOI: 10.1371/journal.pone.0100639.t004

DOI: 10.1371/journal.pone.0100639.t005

DOI: 10.1371/journal.pone.0100639.s001

DOI: 10.1371/journal.pone.0100639.s002

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2014

detail.hit.zdb_id: 2267670-3

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Human CD4+ T Cell Epitopes from Vaccinia Virus Induced by Vaccination or Infection

Calvo-Calle, J. Mauricio ; Strug, Iwona ; Nastke, Maria-Dorothea ; [et al.]

Public Library of Science (PLoS) ; 2007

In: PLoS Pathogens Vol. 3, No. 10 ( 2007-10-12), p. e144-

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In: PLoS Pathogens, Public Library of Science (PLoS), Vol. 3, No. 10 ( 2007-10-12), p. e144-

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.0030144

DOI: 10.1371/journal.ppat.0030144.g001

DOI: 10.1371/journal.ppat.0030144.g002

DOI: 10.1371/journal.ppat.0030144.g003

DOI: 10.1371/journal.ppat.0030144.g004

DOI: 10.1371/journal.ppat.0030144.g005

DOI: 10.1371/journal.ppat.0030144.g006

DOI: 10.1371/journal.ppat.0030144.t001

DOI: 10.1371/journal.ppat.0030144.t002

DOI: 10.1371/journal.ppat.0030144.t003

DOI: 10.1371/journal.ppat.0030144.t004

DOI: 10.1371/journal.ppat.0030144.t005

DOI: 10.1371/journal.ppat.0030144.sg001

DOI: 10.1371/journal.ppat.0030144.sg002

DOI: 10.1371/journal.ppat.0030144.sg003

DOI: 10.1371/journal.ppat.0030144.sg004

DOI: 10.1371/journal.ppat.0030144.sg005

DOI: 10.1371/journal.ppat.0030144.st001

DOI: 10.1371/journal.ppat.0030144.st002

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2007

detail.hit.zdb_id: 2205412-1

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Profiling MHC-I and MHC-II canonical and out-of-frame epitopes from SARS-CoV-2 and seasonal human coronavirus infected human cells

Nanaware, Padma Pandurang ; Becerra-Artiles, Aniuska ; Cruz, John ; [et al.]

The American Association of Immunologists ; 2022

In: The Journal of Immunology Vol. 208, No. 1_Supplement ( 2022-05-01), p. 102.14-102.14

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In: The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 1_Supplement ( 2022-05-01), p. 102.14-102.14

Abstract: Understanding the targets of adaptive immunity to SARS-CoV-2 is essential for vaccine development and interpretation of coronavirus disease 2019 (COVID-19) pathogenesis. SARS-CoV-2 and other human coronaviruses share substantial sequence homology raising the possibility that the previous exposure to seasonal “common cold” human coronaviruses could impact the T cell response upon SARS-CoV-2 infection. Detailed investigation of the antigenic peptides presented in SARS-CoV-2 and other common coronavirus infections would be beneficial to understand the impact of preexisting T cell mediated immunity on SARS-CoV-2 infection. The repertoire of naturally processed and presented viral peptides by MHC II upon SARS-CoV-2 and seasonal human coronaviruses infections remains largely uncharacterized. Here, we report the MHC I and II immunopeptidome of cells infected with SARS-CoV-2 or hCoV-OC43, one of the seasonal coronaviruses. We identified 11 MHC I peptides and 13 MHC II peptides of SARS-CoV-2 infected cells including both canonical and out-of-frame spike epitopes, 27 MHC I and 91 MHC II peptides from membrane, nucleocapsid, spike and hemagglutinin-esterase from OC43 infected cells using mass spectrometry. We validated some peptides using HLA peptide binding assays, and these peptides were shown to recall T cell responses in donors with presumed history of common cold viral infection. Some of these peptides share substantial homology with common cold coronaviruses, indicating possibility of conserved T cell epitopes eliciting the protective immunity in COVID-19. The identification of naturally presented peptides and their striking homology with other coronavirus could aid in the peptide selection for the vaccine development.

Type of Medium: Online Resource

ISSN: 0022-1767 , 1550-6606

URL: Article

DOI: 10.4049/jimmunol.208.Supp.102.14

RVK:

XA 54100

RVK:

XA 10000

Language: English

Publisher: The American Association of Immunologists

Publication Date: 2022

detail.hit.zdb_id: 1475085-5

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PDIA3 epitope-driven immune autoreactivity contributes to hepatic damage in type 2 diabetes

Clement, Cristina C. ; Osan, Jaspreet ; Buque, Aitziber ; [et al.]

American Association for the Advancement of Science (AAAS) ; 2022

In: Science Immunology Vol. 7, No. 74 ( 2022-08-12)

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In: Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 7, No. 74 ( 2022-08-12)

Abstract: So-called “American,” high-fat and high-sugar, diets are known to contribute to chronic inflammation in the liver and subsequent autoimmune reactions, yet the immune responses behind this phenomenon are not well characterized. Here, Clement et al . identified PDIA3, a protein involved in immunogenic cell death, as a peptide presented via MHC-II that led to pathogenic T and B cell responses in mice given a high-fat, high-glucose diet. PDIA3-specific T cells and PDIA3-specific antibodies were sufficient to induce liver toxicity. Anti-PDIA3 was detected at high levels in the serum of patients with chronic inflammatory liver conditions. Thus, the American diet induces liver damage through PDIA3-specific T and B cells in mice.

Type of Medium: Online Resource

ISSN: 2470-9468

URL: Article

DOI: 10.1126/sciimmunol.abl3795

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2022

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Broadly recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles

Becerra-Artiles, Aniuska ; Calvo-Calle, J. Mauricio ; Co, Mary Dawn ; [et al.]

Elsevier BV ; 2022

In: Cell Reports Vol. 39, No. 11 ( 2022-06), p. 110952-

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In: Cell Reports, Elsevier BV, Vol. 39, No. 11 ( 2022-06), p. 110952-

Type of Medium: Online Resource

ISSN: 2211-1247

URL: Article

DOI: 10.1016/j.celrep.2022.110952

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2649101-1

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Effect of adjuvant on reactogenicity and long-term immunogenicity of the malaria Vaccine ICC-1132 in macaques

Langermans, Jan A.M. ; Schmidt, Annette ; Vervenne, Richard A.W. ; [et al.]

Elsevier BV ; 2005

In: Vaccine Vol. 23, No. 41 ( 2005-9), p. 4935-4943

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In: Vaccine, Elsevier BV, Vol. 23, No. 41 ( 2005-9), p. 4935-4943

Type of Medium: Online Resource

ISSN: 0264-410X

URL: Article

DOI: 10.1016/j.vaccine.2005.05.036

Language: English

Publisher: Elsevier BV

Publication Date: 2005

detail.hit.zdb_id: 1468474-3

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Human CD4 + T Cell Response to Human Herpesvirus 6

Nastke, Maria-D. ; Becerra, Aniuska ; Yin, Liusong ; [et al.]

American Society for Microbiology ; 2012

In: Journal of Virology Vol. 86, No. 9 ( 2012-05), p. 4776-4792

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In: Journal of Virology, American Society for Microbiology, Vol. 86, No. 9 ( 2012-05), p. 4776-4792

Abstract: Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4 + T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro . Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-γ) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4 + T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4 + T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.06573-11

Language: English

Publisher: American Society for Microbiology

Publication Date: 2012

detail.hit.zdb_id: 1495529-5

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Immune response to HHV-6 and implications for immunotherapy

Becerra, Aniuska ; Gibson, Laura ; Stern, Lawrence J ; [et al.]

Elsevier BV ; 2014

In: Current Opinion in Virology Vol. 9 ( 2014-12), p. 154-161

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In: Current Opinion in Virology, Elsevier BV, Vol. 9 ( 2014-12), p. 154-161

Type of Medium: Online Resource

ISSN: 1879-6257

URL: Article

DOI: 10.1016/j.coviro.2014.10.001

Language: English

Publisher: Elsevier BV

Publication Date: 2014

detail.hit.zdb_id: 2611378-8

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