MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques

Shelby L. O'Connor; Jennifer J. Lhost; Ericka A. Becker; Ann M. Detmer; Randall C. Johnson; Caitlin E. MacNair; Roger W. Wiseman; Julie A. Karl; Justin M. Greene; Benjamin J. Burwitz; Benjamin N. Bimber; Simon M. Lank; Jennifer J. Tuscher; Edward T. Mee; Nicola J. Rose; Ronald C. Desrosiers; Austin L. Hughes; Thomas C. Friedrich; Mary Carrington; David H. O'Connor

doi:10.1126/scitranslmed.3000524

MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques

Shelby L. O'Connor, Jennifer J. Lhost, Ericka A. Becker, Ann M. Detmer, Randall C. Johnson, Caitlin E. MacNair, Roger W. Wiseman, Julie A. Karl, Justin M. Greene, Benjamin J. Burwitz, Benjamin N. Bimber, Simon M. Lank, Jennifer J. Tuscher, Edward T. Mee, Nicola J. Rose, Ronald C. Desrosiers, Austin L. Hughes, Thomas C. Friedrich, Mary Carrington, David H. O'Connor

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Abstract

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 MHChomozygous 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 epitopespecific 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.

Original language	English (US)
Pages (from-to)	22ra18
Journal	Science translational medicine
Volume	2
Issue number	22
DOIs	https://doi.org/10.1126/scitranslmed.3000524
State	Published - 2010
Externally published	Yes

ASJC Scopus subject areas

Medicine(all)

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O'Connor, S. L., Lhost, J. J., Becker, E. A., Detmer, A. M., Johnson, R. C., MacNair, C. E., Wiseman, R. W., Karl, J. A., Greene, J. M., Burwitz, B. J., Bimber, B. N., Lank, S. M., Tuscher, J. J., Mee, E. T., Rose, N. J., Desrosiers, R. C., Hughes, A. L., Friedrich, T. C., Carrington, M., & O'Connor, D. H. (2010). MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques. Science translational medicine, 2(22), 22ra18. https://doi.org/10.1126/scitranslmed.3000524

O'Connor, SL, Lhost, JJ, Becker, EA, Detmer, AM, Johnson, RC, MacNair, CE, Wiseman, RW, Karl, JA, Greene, JM, Burwitz, BJ , Bimber, BN, Lank, SM, Tuscher, JJ, Mee, ET, Rose, NJ, Desrosiers, RC, Hughes, AL, Friedrich, TC, Carrington, M & O'Connor, DH 2010, 'MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques', Science translational medicine, vol. 2, no. 22, pp. 22ra18. https://doi.org/10.1126/scitranslmed.3000524

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abstract = "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 MHChomozygous 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 epitopespecific 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.",

author = "O'Connor, {Shelby L.} and Lhost, {Jennifer J.} and Becker, {Ericka A.} and Detmer, {Ann M.} and Johnson, {Randall C.} and MacNair, {Caitlin E.} and Wiseman, {Roger W.} and Karl, {Julie A.} and Greene, {Justin M.} and Burwitz, {Benjamin J.} and Bimber, {Benjamin N.} and Lank, {Simon M.} and Tuscher, {Jennifer J.} and Mee, {Edward T.} and Rose, {Nicola J.} and Desrosiers, {Ronald C.} and Hughes, {Austin L.} and Friedrich, {Thomas C.} and Mary Carrington and O'Connor, {David H.}",

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AU - MacNair, Caitlin E.

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AU - Karl, Julie A.

AU - Greene, Justin M.

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AU - Lank, Simon M.

AU - Tuscher, Jennifer J.

AU - Mee, Edward T.

AU - Rose, Nicola J.

AU - Desrosiers, Ronald C.

AU - Hughes, Austin L.

AU - Friedrich, Thomas C.

AU - Carrington, Mary

AU - O'Connor, David H.

PY - 2010

Y1 - 2010

N2 - 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 MHChomozygous 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 epitopespecific 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.

AB - 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 MHChomozygous 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 epitopespecific 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.

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MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques

Abstract

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