Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia.
Identifieur interne : 002E84 ( Main/Exploration ); précédent : 002E83; suivant : 002E85Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia.
Auteurs : Zongdong Li [États-Unis] ; Michael A. Nardi ; Simon KarpatkinSource :
- Blood [ 0006-4971 ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Anticorps anti-VIH, Antigènes du VIH (), Antigènes du VIH (génétique), Banque de peptides, Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire (), Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire (génétique), Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire (immunologie), Femelle, Fragments peptidiques (), Fragments peptidiques (génétique), Fragments peptidiques (immunologie), Humains, Immunisation passive, Infections à VIH (), Infections à VIH (immunologie), Lapins, Mimétisme moléculaire, Oligopeptides (), Oligopeptides (génétique), Oligopeptides (immunologie), Protéines des retroviridae (), Protéines des retroviridae (génétique), Protéines des retroviridae (immunologie), Purpura thrombopénique idiopathique (immunologie), Purpura thrombopénique idiopathique (étiologie), Souris, Souris de lignée BALB C, Séquence d'acides aminés, Techniques in vitro, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie), Épitopes (), Épitopes (génétique).
- MESH :
- génétique : Antigènes du VIH, Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire, Fragments peptidiques, Oligopeptides, Protéines des retroviridae, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Épitopes.
- immunologie : Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire, Fragments peptidiques, Infections à VIH, Oligopeptides, Protéines des retroviridae, Purpura thrombopénique idiopathique, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- étiologie : Purpura thrombopénique idiopathique.
- Animaux, Anticorps anti-VIH, Antigènes du VIH, Banque de peptides, Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire, Femelle, Fragments peptidiques, Humains, Immunisation passive, Infections à VIH, Lapins, Mimétisme moléculaire, Oligopeptides, Protéines des retroviridae, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Techniques in vitro, Épitopes.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Epitopes (chemistry), Epitopes (genetics), Female, HIV Antibodies, HIV Antigens (chemistry), HIV Antigens (genetics), HIV Infections (complications), HIV Infections (immunology), HIV-1 (genetics), HIV-1 (immunology), Humans, Immunization, Passive, In Vitro Techniques, Mice, Mice, Inbred BALB C, Molecular Mimicry, Oligopeptides (chemistry), Oligopeptides (genetics), Oligopeptides (immunology), Peptide Fragments (chemistry), Peptide Fragments (genetics), Peptide Fragments (immunology), Peptide Library, Platelet Glycoprotein GPIIb-IIIa Complex (chemistry), Platelet Glycoprotein GPIIb-IIIa Complex (genetics), Platelet Glycoprotein GPIIb-IIIa Complex (immunology), Purpura, Thrombocytopenic, Idiopathic (etiology), Purpura, Thrombocytopenic, Idiopathic (immunology), Rabbits, Retroviridae Proteins (chemistry), Retroviridae Proteins (genetics), Retroviridae Proteins (immunology).
- MESH :
- chemical , chemistry : Epitopes, HIV Antigens, Oligopeptides, Peptide Fragments, Platelet Glycoprotein GPIIb-IIIa Complex, Retroviridae Proteins.
- chemical , genetics : Epitopes, HIV Antigens, Oligopeptides, Peptide Fragments, Platelet Glycoprotein GPIIb-IIIa Complex, Retroviridae Proteins.
- complications : HIV Infections.
- etiology : Purpura, Thrombocytopenic, Idiopathic.
- genetics : HIV-1.
- immunology : HIV Infections, HIV-1, Oligopeptides, Peptide Fragments, Platelet Glycoprotein GPIIb-IIIa Complex, Purpura, Thrombocytopenic, Idiopathic, Retroviridae Proteins.
- Amino Acid Sequence, Animals, Female, HIV Antibodies, Humans, Immunization, Passive, In Vitro Techniques, Mice, Mice, Inbred BALB C, Molecular Mimicry, Peptide Library, Rabbits.
Abstract
Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the beta3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti-GPIIIa49-66-induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated.
DOI: 10.1182/blood-2005-01-0243
PubMed: 15774614
Affiliations:
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Le document en format XML
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<term>Epitopes (genetics)</term>
<term>Female</term>
<term>HIV Antibodies</term>
<term>HIV Antigens (chemistry)</term>
<term>HIV Antigens (genetics)</term>
<term>HIV Infections (complications)</term>
<term>HIV Infections (immunology)</term>
<term>HIV-1 (genetics)</term>
<term>HIV-1 (immunology)</term>
<term>Humans</term>
<term>Immunization, Passive</term>
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<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Mimicry</term>
<term>Oligopeptides (chemistry)</term>
<term>Oligopeptides (genetics)</term>
<term>Oligopeptides (immunology)</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Peptide Library</term>
<term>Platelet Glycoprotein GPIIb-IIIa Complex (chemistry)</term>
<term>Platelet Glycoprotein GPIIb-IIIa Complex (genetics)</term>
<term>Platelet Glycoprotein GPIIb-IIIa Complex (immunology)</term>
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<term>Purpura, Thrombocytopenic, Idiopathic (immunology)</term>
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<term>Anticorps anti-VIH</term>
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<term>Antigènes du VIH (génétique)</term>
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<term>Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire (génétique)</term>
<term>Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire (immunologie)</term>
<term>Femelle</term>
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<term>Fragments peptidiques (génétique)</term>
<term>Fragments peptidiques (immunologie)</term>
<term>Humains</term>
<term>Immunisation passive</term>
<term>Infections à VIH ()</term>
<term>Infections à VIH (immunologie)</term>
<term>Lapins</term>
<term>Mimétisme moléculaire</term>
<term>Oligopeptides ()</term>
<term>Oligopeptides (génétique)</term>
<term>Oligopeptides (immunologie)</term>
<term>Protéines des retroviridae ()</term>
<term>Protéines des retroviridae (génétique)</term>
<term>Protéines des retroviridae (immunologie)</term>
<term>Purpura thrombopénique idiopathique (immunologie)</term>
<term>Purpura thrombopénique idiopathique (étiologie)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Techniques in vitro</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term>
<term>Épitopes ()</term>
<term>Épitopes (génétique)</term>
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<term>HIV Antigens</term>
<term>Oligopeptides</term>
<term>Peptide Fragments</term>
<term>Platelet Glycoprotein GPIIb-IIIa Complex</term>
<term>Retroviridae Proteins</term>
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<term>HIV Antigens</term>
<term>Oligopeptides</term>
<term>Peptide Fragments</term>
<term>Platelet Glycoprotein GPIIb-IIIa Complex</term>
<term>Retroviridae Proteins</term>
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<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>HIV Infections</term>
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<term>Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire</term>
<term>Fragments peptidiques</term>
<term>Oligopeptides</term>
<term>Protéines des retroviridae</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
<term>Épitopes</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire</term>
<term>Fragments peptidiques</term>
<term>Infections à VIH</term>
<term>Oligopeptides</term>
<term>Protéines des retroviridae</term>
<term>Purpura thrombopénique idiopathique</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>HIV Infections</term>
<term>HIV-1</term>
<term>Oligopeptides</term>
<term>Peptide Fragments</term>
<term>Platelet Glycoprotein GPIIb-IIIa Complex</term>
<term>Purpura, Thrombocytopenic, Idiopathic</term>
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<term>Female</term>
<term>HIV Antibodies</term>
<term>Humans</term>
<term>Immunization, Passive</term>
<term>In Vitro Techniques</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Mimicry</term>
<term>Peptide Library</term>
<term>Rabbits</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Anticorps anti-VIH</term>
<term>Antigènes du VIH</term>
<term>Banque de peptides</term>
<term>Complexe glycoprotéique IIb-IIIa de la membrane plaquettaire</term>
<term>Femelle</term>
<term>Fragments peptidiques</term>
<term>Humains</term>
<term>Immunisation passive</term>
<term>Infections à VIH</term>
<term>Lapins</term>
<term>Mimétisme moléculaire</term>
<term>Oligopeptides</term>
<term>Protéines des retroviridae</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Techniques in vitro</term>
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<front><div type="abstract" xml:lang="en">Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the beta3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti-GPIIIa49-66-induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated.</div>
</front>
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<region><li>État de New York</li>
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<tree><noCountry><name sortKey="Karpatkin, Simon" sort="Karpatkin, Simon" uniqKey="Karpatkin S" first="Simon" last="Karpatkin">Simon Karpatkin</name>
<name sortKey="Nardi, Michael A" sort="Nardi, Michael A" uniqKey="Nardi M" first="Michael A" last="Nardi">Michael A. Nardi</name>
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<country name="États-Unis"><region name="État de New York"><name sortKey="Li, Zongdong" sort="Li, Zongdong" uniqKey="Li Z" first="Zongdong" last="Li">Zongdong Li</name>
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