Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02: A paradigm for virus evolution and persistence?

Thorsten U. Vogel, Thomas C. Friedrich, David H. O'Connor, William Rehrauer, Elizabeth J. Dodds, Heather Hickman, William Hildebrand, John Sidney, Alessandro Sette, Austin Hughes, Helen Horton, Kathy Vielhuber, Richard Rudersdorf, Ivna P. De Souza, Matthew R. Reynolds, Todd M. Allen, Nancy Wilson, David Watkins

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79 GY9), and one from the Nef protein (Nef159-167 YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two epitopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167 YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79 GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35 SLS, which reproducibly selects for escape variants during acute infection, and Gag181-189 CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.

Original languageEnglish
Pages (from-to)11623-11636
Number of pages14
JournalJournal of Virology
Volume76
Issue number22
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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cytotoxic T-lymphocytes
T-Lymphocyte Epitopes
major histocompatibility complex
Cytotoxic T-Lymphocytes
Major Histocompatibility Complex
epitopes
Viruses
viruses
Epitopes
Macaca
Simian immunodeficiency virus
Simian Immunodeficiency Virus
immunosuppression
nef Gene Products
vaccines
AIDS Vaccines
Virus Diseases
Virus Replication
virus replication
Macaca mulatta

ASJC Scopus subject areas

  • Immunology

Cite this

Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02 : A paradigm for virus evolution and persistence? / Vogel, Thorsten U.; Friedrich, Thomas C.; O'Connor, David H.; Rehrauer, William; Dodds, Elizabeth J.; Hickman, Heather; Hildebrand, William; Sidney, John; Sette, Alessandro; Hughes, Austin; Horton, Helen; Vielhuber, Kathy; Rudersdorf, Richard; De Souza, Ivna P.; Reynolds, Matthew R.; Allen, Todd M.; Wilson, Nancy; Watkins, David.

In: Journal of Virology, Vol. 76, No. 22, 01.11.2002, p. 11623-11636.

Research output: Contribution to journalArticle

Vogel, TU, Friedrich, TC, O'Connor, DH, Rehrauer, W, Dodds, EJ, Hickman, H, Hildebrand, W, Sidney, J, Sette, A, Hughes, A, Horton, H, Vielhuber, K, Rudersdorf, R, De Souza, IP, Reynolds, MR, Allen, TM, Wilson, N & Watkins, D 2002, 'Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02: A paradigm for virus evolution and persistence?', Journal of Virology, vol. 76, no. 22, pp. 11623-11636. https://doi.org/10.1128/JVI.76.22.11623-11636.2002
Vogel, Thorsten U. ; Friedrich, Thomas C. ; O'Connor, David H. ; Rehrauer, William ; Dodds, Elizabeth J. ; Hickman, Heather ; Hildebrand, William ; Sidney, John ; Sette, Alessandro ; Hughes, Austin ; Horton, Helen ; Vielhuber, Kathy ; Rudersdorf, Richard ; De Souza, Ivna P. ; Reynolds, Matthew R. ; Allen, Todd M. ; Wilson, Nancy ; Watkins, David. / Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02 : A paradigm for virus evolution and persistence?. In: Journal of Virology. 2002 ; Vol. 76, No. 22. pp. 11623-11636.
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abstract = "It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79 GY9), and one from the Nef protein (Nef159-167 YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two epitopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167 YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79 GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35 SLS, which reproducibly selects for escape variants during acute infection, and Gag181-189 CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.",
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AU - Friedrich, Thomas C.

AU - O'Connor, David H.

AU - Rehrauer, William

AU - Dodds, Elizabeth J.

AU - Hickman, Heather

AU - Hildebrand, William

AU - Sidney, John

AU - Sette, Alessandro

AU - Hughes, Austin

AU - Horton, Helen

AU - Vielhuber, Kathy

AU - Rudersdorf, Richard

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AU - Wilson, Nancy

AU - Watkins, David

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