MHC Heterozygote Advantage in Simian Immunodeficiency Virus-Infected Mauritian Cynomolgus Macaques

被引：70

作者：

O'Connor, Shelby L. ^{[1
]}

Lhost, Jennifer J. ^{[1
]}

Becker, Ericka A. ^{[2
]}

Detmer, Ann M. ^{[2
]}

Johnson, Randall C. ^{[3
,4
]}

MacNair, Caitlin E. ^{[2
]}

Wiseman, Roger W. ^{[2
]}

Karl, Julie A. ^{[2
]}

Greene, Justin M. ^{[1
]}

Burwitz, Benjamin J. ^{[1
]}

Bimber, Benjamin N. ^{[2
]}

Lank, Simon M. ^{[2
]}

Tuscher, Jennifer J. ^{[2
]}

Mee, Edward T. ^{[5
]}

Rose, Nicola J. ^{[5
]}

Desrosiers, Ronald C. ^{[6
]}

Hughes, Austin L. ^{[7
]}

Friedrich, Thomas C. ^{[2
]}

Carrington, Mary ^{[8
,9
]}

O'Connor, David H. ^{[1
,2
]}

机构：

[1] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA

[2] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA

[3] NCI, Lab Genom Divers, Sci Applicat Int Corp, Frederick, MD 21702 USA

[4] Conservatoire Natl Arts & Metiers, Chaire Bioinfromat, F-75003 Paris, France

[5] Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England

[6] Harvard Univ, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA

[7] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA

[8] NCI, Canc & Inflammat Program, Sci Applicat Int Corp, Frederick, MD 21702 USA

[9] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2010年 / 2卷 / 22期

基金：

英国医学研究理事会;

关键词：

T-CELL RESPONSES; CLASS-I ALLELES; VIRAL LOAD; LYMPHOCYTE ESCAPE; HIV-1; EVOLUTION; VACCINE; HLA; TYPE-1; REPLICATION; NEUTRALIZATION;

D O I：

10.1126/scitranslmed.3000524

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)-infected major histocompatibility complex (MHC)-homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.

引用

页数：9

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