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The recognition of a viral antigenic moiety by class I MHC-restricted cytolytic T lymphocytes is limited by the availability of the endogenously processed antigen.

Identifieur interne : 000187 ( Ncbi/Curation ); précédent : 000186; suivant : 000188

The recognition of a viral antigenic moiety by class I MHC-restricted cytolytic T lymphocytes is limited by the availability of the endogenously processed antigen.

Auteurs : G N Milligan [États-Unis] ; L A Morrison ; J. Gorka ; V L Braciale ; T J Braciale

Source :

RBID : pubmed:1700000

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English descriptors

Abstract

The transmembrane hydrophobic domain of the type A influenza A/JAPAN/305/57 (H2N2) hemagglutinin (HA) contains an immunodominant site encompassing amino acids 523-545 (J523-545) recognized by class I MHC-restricted cytolytic T lymphocytes (CTL). Class I CTL of two fine specificity subsets map to this transmembrane (TM) site. One of these CTL subpopulations is subtype specific. These T lymphocytes recognize the site generated during infection of target cells with A/JAPAN/305/57 virus (H2N2) but not target cells expressing the comparable TM site of the influenza A/PR/8/34 virus (H1N1) hemagglutinin (P527-549) after infection with this virus. The other CTL subpopulation is cross-reactive and recognizes the TM site of the A/JAPAN/305/57 HA and the A/PR/8/34 HA with similar efficiency. Analyses of the critical amino acids in the TM site necessary for CTL recognition with the use of synthetic peptides unexpectedly revealed reactivity for the A/PR/8 HA TM site by subtype-specific CTL. This reactivity was only observed with truncated peptides corresponding to a limited portion of the A/PR/8 HA TM site but also required peptide concentrations greater than 10(-7) M. These results suggested either that the endogenously processed A/PR/8 HA TM site generated during infection was larger than the site defined by the truncated cross-reactive peptides or that the concentration of endogenously processed TM site produced during infection was limiting. To distinguish between these possibilities, we expressed in target cells synthetic minigenes encoding only the portion of the A/PR/8 HA transmembrane sites defined by the synthetic peptides. Unlike the peptides, the "preprocessed" endogenous minigene products were not recognized by subtype-specific CTL. These data suggest that the level of available endogenously processed Ag rather than selectivity in the site of fragmentation of newly synthesized Ag may play a critical role in determining whether the complex of the antigenic moiety and class I MHC is efficiently presented to and recognized by class I CTL.

PubMed: 1700000

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Le document en format XML

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<nlm:affiliation>Department of Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<wicri:cityArea>Department of Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis</wicri:cityArea>
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<name sortKey="Morrison, L A" sort="Morrison, L A" uniqKey="Morrison L" first="L A" last="Morrison">L A Morrison</name>
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<name sortKey="Braciale, V L" sort="Braciale, V L" uniqKey="Braciale V" first="V L" last="Braciale">V L Braciale</name>
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<title level="j">Journal of immunology (Baltimore, Md. : 1950)</title>
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<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Antigens, Viral (immunology)</term>
<term>Epitopes</term>
<term>Female</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Hemagglutinins, Viral (genetics)</term>
<term>Hemagglutinins, Viral (immunology)</term>
<term>Hemagglutinins, Viral (physiology)</term>
<term>Histocompatibility Antigens Class I (immunology)</term>
<term>Influenza A virus (immunology)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Peptides (immunology)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
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<term>Animaux</term>
<term>Antigènes d'histocompatibilité de classe I (immunologie)</term>
<term>Antigènes viraux (immunologie)</term>
<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Hémagglutinines virales (génétique)</term>
<term>Hémagglutinines virales (immunologie)</term>
<term>Hémagglutinines virales (physiologie)</term>
<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Peptides (immunologie)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Virus de la grippe A (immunologie)</term>
<term>Épitopes</term>
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<term>Hemagglutinins, Viral</term>
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<term>Antigens, Viral</term>
<term>Hemagglutinins, Viral</term>
<term>Histocompatibility Antigens Class I</term>
<term>Peptides</term>
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<term>Hemagglutinins, Viral</term>
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<term>Hémagglutinines virales</term>
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<term>Antigènes d'histocompatibilité de classe I</term>
<term>Antigènes viraux</term>
<term>Hémagglutinines virales</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Peptides</term>
<term>Virus de la grippe A</term>
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<term>Influenza A virus</term>
<term>T-Lymphocytes, Cytotoxic</term>
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<term>Hémagglutinines virales</term>
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<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Epitopes</term>
<term>Female</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
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<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Glycoprotéine hémagglutinine du virus influenza</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
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<div type="abstract" xml:lang="en">The transmembrane hydrophobic domain of the type A influenza A/JAPAN/305/57 (H2N2) hemagglutinin (HA) contains an immunodominant site encompassing amino acids 523-545 (J523-545) recognized by class I MHC-restricted cytolytic T lymphocytes (CTL). Class I CTL of two fine specificity subsets map to this transmembrane (TM) site. One of these CTL subpopulations is subtype specific. These T lymphocytes recognize the site generated during infection of target cells with A/JAPAN/305/57 virus (H2N2) but not target cells expressing the comparable TM site of the influenza A/PR/8/34 virus (H1N1) hemagglutinin (P527-549) after infection with this virus. The other CTL subpopulation is cross-reactive and recognizes the TM site of the A/JAPAN/305/57 HA and the A/PR/8/34 HA with similar efficiency. Analyses of the critical amino acids in the TM site necessary for CTL recognition with the use of synthetic peptides unexpectedly revealed reactivity for the A/PR/8 HA TM site by subtype-specific CTL. This reactivity was only observed with truncated peptides corresponding to a limited portion of the A/PR/8 HA TM site but also required peptide concentrations greater than 10(-7) M. These results suggested either that the endogenously processed A/PR/8 HA TM site generated during infection was larger than the site defined by the truncated cross-reactive peptides or that the concentration of endogenously processed TM site produced during infection was limiting. To distinguish between these possibilities, we expressed in target cells synthetic minigenes encoding only the portion of the A/PR/8 HA transmembrane sites defined by the synthetic peptides. Unlike the peptides, the "preprocessed" endogenous minigene products were not recognized by subtype-specific CTL. These data suggest that the level of available endogenously processed Ag rather than selectivity in the site of fragmentation of newly synthesized Ag may play a critical role in determining whether the complex of the antigenic moiety and class I MHC is efficiently presented to and recognized by class I CTL.</div>
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