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Pathogenesis and Immunity

Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses

David H. O'Connor, Bianca R. Mothe, Jason T. Weinfurter, Sarah Fuenger, William M. Rehrauer, Peicheng Jing, Richard R. Rudersdorf, Max E. Liebl, Kendall Krebs, Joshua Vasquez, Elizabeth Dodds, John Loffredo, Sarah Martin, Adrian B. McDermott, Todd M. Allen, Chenxi Wang, G. G. Doxiadis, David C. Montefiori, Austin Hughes, Dennis R. Burton, David B. Allison, Steven M. Wolinsky, Ronald Bontrop, Louis J. Picker, David I. Watkins
David H. O'Connor
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Bianca R. Mothe
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Jason T. Weinfurter
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Sarah Fuenger
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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William M. Rehrauer
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Peicheng Jing
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Richard R. Rudersdorf
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Max E. Liebl
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Kendall Krebs
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Joshua Vasquez
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Elizabeth Dodds
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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John Loffredo
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Sarah Martin
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Adrian B. McDermott
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Todd M. Allen
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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Chenxi Wang
2University of Alabama at Birmingham, Birmingham, Alabama
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G. G. Doxiadis
3Biomedical Primate Research Centre-TNO, Rijswijk, The Netherlands
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David C. Montefiori
4Duke University Department of Experimental Surgery, Durham, North Carolina
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Austin Hughes
5University of South Carolina, Columbia, South Carolina
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Dennis R. Burton
6The Scripps Research Institute, La Jolla, California
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David B. Allison
2University of Alabama at Birmingham, Birmingham, Alabama
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Steven M. Wolinsky
7Northwestern University Medical School, Chicago, Illinois
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Ronald Bontrop
3Biomedical Primate Research Centre-TNO, Rijswijk, The Netherlands
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Louis J. Picker
8Oregon Health & Science University Vaccine and Gene Therapy Institute, Portland, Oregon
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David I. Watkins
1Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin
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  • For correspondence: watkins@primate.wisc.edu
DOI: 10.1128/JVI.77.16.9029-9040.2003
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ABSTRACT

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIVmac239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression. We show that the dominant acute-phase cytotoxic T lymphocyte (CTL) responses in animals expressing these alleles are largely directed against two epitopes restricted by Mamu-A*01 and one epitope restricted by Mamu-B*17. One Mamu-A*01-restricted response (Tat28-35SL8) and the Mamu-B*17-restricted response (Nef165-173IW9) typically select for viral escape variants in early SIVmac239 infection. Interestingly, animals expressing Mamu-A*1 and -B*17 have less variation in the Tat28-35SL8 epitope during chronic infection than animals that express only Mamu-A*01. Our results show that MHC-I alleles that are associated with slow progression to AIDS bind epitopes recognized by dominant CTL responses during acute infection and underscore the importance of understanding CTL responses during primary HIV infection.

  • Copyright © 2003 American Society for Microbiology
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Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses
David H. O'Connor, Bianca R. Mothe, Jason T. Weinfurter, Sarah Fuenger, William M. Rehrauer, Peicheng Jing, Richard R. Rudersdorf, Max E. Liebl, Kendall Krebs, Joshua Vasquez, Elizabeth Dodds, John Loffredo, Sarah Martin, Adrian B. McDermott, Todd M. Allen, Chenxi Wang, G. G. Doxiadis, David C. Montefiori, Austin Hughes, Dennis R. Burton, David B. Allison, Steven M. Wolinsky, Ronald Bontrop, Louis J. Picker, David I. Watkins
Journal of Virology Jul 2003, 77 (16) 9029-9040; DOI: 10.1128/JVI.77.16.9029-9040.2003

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Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses
David H. O'Connor, Bianca R. Mothe, Jason T. Weinfurter, Sarah Fuenger, William M. Rehrauer, Peicheng Jing, Richard R. Rudersdorf, Max E. Liebl, Kendall Krebs, Joshua Vasquez, Elizabeth Dodds, John Loffredo, Sarah Martin, Adrian B. McDermott, Todd M. Allen, Chenxi Wang, G. G. Doxiadis, David C. Montefiori, Austin Hughes, Dennis R. Burton, David B. Allison, Steven M. Wolinsky, Ronald Bontrop, Louis J. Picker, David I. Watkins
Journal of Virology Jul 2003, 77 (16) 9029-9040; DOI: 10.1128/JVI.77.16.9029-9040.2003
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KEYWORDS

Alleles
epitopes
Genes, MHC Class I
Simian Acquired Immunodeficiency Syndrome
T-Lymphocytes, Cytotoxic

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