MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques.
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.
O'Connor
Shelby L
SL
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
Lhost
Jennifer J
JJ
Becker
Ericka A
EA
Detmer
Ann M
AM
Johnson
Randall C
RC
Macnair
Caitlin E
CE
Wiseman
Roger W
RW
Karl
Julie A
JA
Greene
Justin M
JM
Burwitz
Benjamin J
BJ
Bimber
Benjamin N
BN
Lank
Simon M
SM
Tuscher
Jennifer J
JJ
Mee
Edward T
ET
Rose
Nicola J
NJ
Desrosiers
Ronald C
RC
Hughes
Austin L
AL
Friedrich
Thomas C
TC
Carrington
Mary
M
O'Connor
David H
DH
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D008252:Macaca fascicularis / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008436:Mauritius; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D014766:Viremia / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000821:virology