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Escape from highly effective public CD8+ T-cell clonotypes by HIV

Identifieur interne : 006161 ( Main/Exploration ); précédent : 006160; suivant : 006162

Escape from highly effective public CD8+ T-cell clonotypes by HIV

Auteurs : Maria Candela Iglesias [France] ; Jorge R. Almeida [France, États-Unis] ; Solène Fastenackels [France] ; David J. Van Bockel [Australie] ; Masao Hashimoto [Japon] ; Vanessa Venturi [Australie] ; Emma Gostick [Royaume-Uni] ; Alejandra Urrutia [France] ; Linda Wooldridge [Royaume-Uni] ; Mathew Clement [Royaume-Uni] ; Stéphanie Gras [Australie] ; Pascal G. Wilmann [Australie] ; Brigitte Autran [France] ; Arnaud Moris [France] ; Jamie Rossjohn [Australie] ; Miles P. Davenport [Australie] ; Masafumi Takiguchi [Japon] ; Christian Brander [Espagne] ; Daniel C. Douek [États-Unis] ; Anthony D. Kelleher [Australie] ; David A. Price [États-Unis, Royaume-Uni] ; Victor Appay [France]

Source :

RBID : PMC:3162351

Abstract

Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8+ T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8+ T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These “public” clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L268M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8+ T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8+ T-cell response against HIV.


Url:
DOI: 10.1182/blood-2011-01-328781
PubMed: 21734237
PubMed Central: 3162351


Affiliations:


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Le document en format XML

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<name sortKey="Van Bockel, David J" sort="Van Bockel, David J" uniqKey="Van Bockel D" first="David J." last="Van Bockel">David J. Van Bockel</name>
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<nlm:aff id="aff3">St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</nlm:aff>
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</author>
<author>
<name sortKey="Hashimoto, Masao" sort="Hashimoto, Masao" uniqKey="Hashimoto M" first="Masao" last="Hashimoto">Masao Hashimoto</name>
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<nlm:aff id="aff4">Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto</wicri:regionArea>
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</author>
<author>
<name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name>
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<nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington</wicri:regionArea>
<wicri:noRegion>Kensington</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Urrutia, Alejandra" sort="Urrutia, Alejandra" uniqKey="Urrutia A" first="Alejandra" last="Urrutia">Alejandra Urrutia</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Clement, Mathew" sort="Clement, Mathew" uniqKey="Clement M" first="Mathew" last="Clement">Mathew Clement</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stéphanie" last="Gras">Stéphanie Gras</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Wilmann, Pascal G" sort="Wilmann, Pascal G" uniqKey="Wilmann P" first="Pascal G." last="Wilmann">Pascal G. Wilmann</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff8">AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name>
<affiliation wicri:level="1">
<nlm:aff id="aff9">Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington</wicri:regionArea>
<wicri:noRegion>Kensington</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Takiguchi, Masafumi" sort="Takiguchi, Masafumi" uniqKey="Takiguchi M" first="Masafumi" last="Takiguchi">Masafumi Takiguchi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff4">Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto</wicri:regionArea>
<wicri:noRegion>Kumamoto</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name>
<affiliation wicri:level="3">
<nlm:aff wicri:cut="; and" id="aff10">AIDS Research Institute IrsiCaixa–HIVACAT, Hospital Universitari Germans Trias i Pujol Ctra del Canyet, Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>AIDS Research Institute IrsiCaixa–HIVACAT, Hospital Universitari Germans Trias i Pujol Ctra del Canyet, Barcelona</wicri:regionArea>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff11">Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona</wicri:regionArea>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name>
<affiliation wicri:level="2">
<nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst</wicri:regionArea>
<wicri:noRegion>Darlinghurst</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name>
<affiliation wicri:level="2">
<nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff</wicri:regionArea>
<wicri:noRegion>Cardiff</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Appay, Victor" sort="Appay, Victor" uniqKey="Appay V" first="Victor" last="Appay">Victor Appay</name>
<affiliation wicri:level="3">
<nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff8">AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8
<sup>+</sup>
T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8
<sup>+</sup>
T-cell clonotypes, characterized by
<italic>TRBV4-3/TRBJ1-3</italic>
gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These “public” clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L
<sub>268</sub>
M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8
<sup>+</sup>
T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8
<sup>+</sup>
T-cell response against HIV.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Espagne</li>
<li>France</li>
<li>Japon</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Catalogne</li>
<li>Maryland</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Barcelone</li>
<li>Paris</li>
</settlement>
</list>
<tree>
<country name="France">
<region name="Île-de-France">
<name sortKey="Iglesias, Maria Candela" sort="Iglesias, Maria Candela" uniqKey="Iglesias M" first="Maria Candela" last="Iglesias">Maria Candela Iglesias</name>
</region>
<name sortKey="Almeida, Jorge R" sort="Almeida, Jorge R" uniqKey="Almeida J" first="Jorge R." last="Almeida">Jorge R. Almeida</name>
<name sortKey="Appay, Victor" sort="Appay, Victor" uniqKey="Appay V" first="Victor" last="Appay">Victor Appay</name>
<name sortKey="Appay, Victor" sort="Appay, Victor" uniqKey="Appay V" first="Victor" last="Appay">Victor Appay</name>
<name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name>
<name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name>
<name sortKey="Fastenackels, Solene" sort="Fastenackels, Solene" uniqKey="Fastenackels S" first="Solène" last="Fastenackels">Solène Fastenackels</name>
<name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name>
<name sortKey="Urrutia, Alejandra" sort="Urrutia, Alejandra" uniqKey="Urrutia A" first="Alejandra" last="Urrutia">Alejandra Urrutia</name>
</country>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Almeida, Jorge R" sort="Almeida, Jorge R" uniqKey="Almeida J" first="Jorge R." last="Almeida">Jorge R. Almeida</name>
</region>
<name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name>
<name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Van Bockel, David J" sort="Van Bockel, David J" uniqKey="Van Bockel D" first="David J." last="Van Bockel">David J. Van Bockel</name>
</noRegion>
<name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name>
<name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stéphanie" last="Gras">Stéphanie Gras</name>
<name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name>
<name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name>
<name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name>
<name sortKey="Wilmann, Pascal G" sort="Wilmann, Pascal G" uniqKey="Wilmann P" first="Pascal G." last="Wilmann">Pascal G. Wilmann</name>
</country>
<country name="Japon">
<noRegion>
<name sortKey="Hashimoto, Masao" sort="Hashimoto, Masao" uniqKey="Hashimoto M" first="Masao" last="Hashimoto">Masao Hashimoto</name>
</noRegion>
<name sortKey="Takiguchi, Masafumi" sort="Takiguchi, Masafumi" uniqKey="Takiguchi M" first="Masafumi" last="Takiguchi">Masafumi Takiguchi</name>
</country>
<country name="Royaume-Uni">
<noRegion>
<name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name>
</noRegion>
<name sortKey="Clement, Mathew" sort="Clement, Mathew" uniqKey="Clement M" first="Mathew" last="Clement">Mathew Clement</name>
<name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name>
<name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name>
</country>
<country name="Espagne">
<region name="Catalogne">
<name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name>
</region>
<name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name>
</country>
</tree>
</affiliations>
</record>

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