Oxidative stress can alter the antigenicity of immunodominant peptides

Daniela Weiskopf; Angelika Schwanninger; Birgit Weinberger; Giovanni Almanzar; Walther Parson; Søren Buus; Herbert Lindner; Beatrix Grubeck-Loebenstein

doi:10.1189/jlb.0209065

Oxidative stress can alter the antigenicity of immunodominant peptides

Daniela Weiskopf, Angelika Schwanninger, Birgit Weinberger, Giovanni Almanzar, Walther Parson, Søren Buus, Herbert Lindner, Beatrix Grubeck-Loebenstein

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

35 Citationer (Scopus)

Abstract

Udgivelsesdato: 2010-Jan

Originalsprog	Engelsk
Tidsskrift	Journal of Leukocyte Biology
Vol/bind	87
Udgave nummer	1
Sider (fra-til)	165-72
Antal sider	8
ISSN	0741-5400
DOI	https://doi.org/10.1189/jlb.0209065
Status	Udgivet - 2010

Bibliografisk note

Keywords: Adult; Amino Acid Motifs; Antigen-Presenting Cells; Antigens, Viral; CD8-Positive T-Lymphocytes; Cells, Cultured; Cytomegalovirus Infections; Female; HLA-A Antigens; Humans; Hydrogen Peroxide; Immunodominant Epitopes; Interferon-gamma; Lymphocyte Activation; Male; Methionine; Oxidation-Reduction; Oxidative Stress; Peptide Fragments; Phosphoproteins; Receptors, Antigen, T-Cell, alpha-beta; Viral Matrix Proteins

Adgang til dokumentet

10.1189/jlb.0209065

Citationsformater

@article{9f51c460779611df928f000ea68e967b,

title = "Oxidative stress can alter the antigenicity of immunodominant peptides",

abstract = "APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic proteins and peptides. Little information is available presently about the consequences of such modifications on the immune response. To model oxidative modification of an immunodominant antigenic peptide, we oxidized the methionine residue of the human CMV pp65(495-503) (NLVPMVATV) peptide. Such modifications of an antigenic peptide can affect MHC binding or TCR recognition. Using binding and dissociation assays, we demonstrate that oxidative modification of the CMVpp65(495-503) peptide leads to a decreased binding of the pMHC complex to the TCR, whereas binding of the peptide to the MHC class I molecule is not impaired. Additionally, we show that CD8(+) T cells have a decreased proliferation and IFN-gamma production when stimulated with oxidized CMVpp65(495-503) peptide. Spectratyping the antigen-binding site of the TCR of responding T cells demonstrates that the CMVpp65(495-503) and the CMVoxpp65(495-503) peptides preferentially stimulate BV8 T cells. Sequencing of this dominant BV family reveals a highly conserved CDR3 amino acid motif, independent of the mode of stimulation, demonstrating the recruitment of the same T cell clonotypes. Our results suggest that oxidative modification of antigenic peptides may affect T cell responses severely by binding T cell clones with different affinity. This may lead to an altered immune response against infectious agents as well as against tumor or autoantigens under oxidative stress conditions.",

author = "Daniela Weiskopf and Angelika Schwanninger and Birgit Weinberger and Giovanni Almanzar and Walther Parson and S{\o}ren Buus and Herbert Lindner and Beatrix Grubeck-Loebenstein",

note = "Keywords: Adult; Amino Acid Motifs; Antigen-Presenting Cells; Antigens, Viral; CD8-Positive T-Lymphocytes; Cells, Cultured; Cytomegalovirus Infections; Female; HLA-A Antigens; Humans; Hydrogen Peroxide; Immunodominant Epitopes; Interferon-gamma; Lymphocyte Activation; Male; Methionine; Oxidation-Reduction; Oxidative Stress; Peptide Fragments; Phosphoproteins; Receptors, Antigen, T-Cell, alpha-beta; Viral Matrix Proteins",

year = "2010",

doi = "10.1189/jlb.0209065",

language = "English",

volume = "87",

pages = "165--72",

journal = "Journal of Leukocyte Biology",

issn = "0741-5400",

publisher = "Federation of American Societies for Experimental Biology",

number = "1",

}

TY - JOUR

T1 - Oxidative stress can alter the antigenicity of immunodominant peptides

AU - Weiskopf, Daniela

AU - Schwanninger, Angelika

AU - Weinberger, Birgit

AU - Almanzar, Giovanni

AU - Parson, Walther

AU - Buus, Søren

AU - Lindner, Herbert

AU - Grubeck-Loebenstein, Beatrix

N1 - Keywords: Adult; Amino Acid Motifs; Antigen-Presenting Cells; Antigens, Viral; CD8-Positive T-Lymphocytes; Cells, Cultured; Cytomegalovirus Infections; Female; HLA-A Antigens; Humans; Hydrogen Peroxide; Immunodominant Epitopes; Interferon-gamma; Lymphocyte Activation; Male; Methionine; Oxidation-Reduction; Oxidative Stress; Peptide Fragments; Phosphoproteins; Receptors, Antigen, T-Cell, alpha-beta; Viral Matrix Proteins

PY - 2010

Y1 - 2010

N2 - APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic proteins and peptides. Little information is available presently about the consequences of such modifications on the immune response. To model oxidative modification of an immunodominant antigenic peptide, we oxidized the methionine residue of the human CMV pp65(495-503) (NLVPMVATV) peptide. Such modifications of an antigenic peptide can affect MHC binding or TCR recognition. Using binding and dissociation assays, we demonstrate that oxidative modification of the CMVpp65(495-503) peptide leads to a decreased binding of the pMHC complex to the TCR, whereas binding of the peptide to the MHC class I molecule is not impaired. Additionally, we show that CD8(+) T cells have a decreased proliferation and IFN-gamma production when stimulated with oxidized CMVpp65(495-503) peptide. Spectratyping the antigen-binding site of the TCR of responding T cells demonstrates that the CMVpp65(495-503) and the CMVoxpp65(495-503) peptides preferentially stimulate BV8 T cells. Sequencing of this dominant BV family reveals a highly conserved CDR3 amino acid motif, independent of the mode of stimulation, demonstrating the recruitment of the same T cell clonotypes. Our results suggest that oxidative modification of antigenic peptides may affect T cell responses severely by binding T cell clones with different affinity. This may lead to an altered immune response against infectious agents as well as against tumor or autoantigens under oxidative stress conditions.

AB - APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic proteins and peptides. Little information is available presently about the consequences of such modifications on the immune response. To model oxidative modification of an immunodominant antigenic peptide, we oxidized the methionine residue of the human CMV pp65(495-503) (NLVPMVATV) peptide. Such modifications of an antigenic peptide can affect MHC binding or TCR recognition. Using binding and dissociation assays, we demonstrate that oxidative modification of the CMVpp65(495-503) peptide leads to a decreased binding of the pMHC complex to the TCR, whereas binding of the peptide to the MHC class I molecule is not impaired. Additionally, we show that CD8(+) T cells have a decreased proliferation and IFN-gamma production when stimulated with oxidized CMVpp65(495-503) peptide. Spectratyping the antigen-binding site of the TCR of responding T cells demonstrates that the CMVpp65(495-503) and the CMVoxpp65(495-503) peptides preferentially stimulate BV8 T cells. Sequencing of this dominant BV family reveals a highly conserved CDR3 amino acid motif, independent of the mode of stimulation, demonstrating the recruitment of the same T cell clonotypes. Our results suggest that oxidative modification of antigenic peptides may affect T cell responses severely by binding T cell clones with different affinity. This may lead to an altered immune response against infectious agents as well as against tumor or autoantigens under oxidative stress conditions.

U2 - 10.1189/jlb.0209065

DO - 10.1189/jlb.0209065

M3 - Journal article

C2 - 19801502

SN - 0741-5400

VL - 87

SP - 165

EP - 172

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

IS - 1

ER -