CD8+ lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule Mamu-A*01

Implications for vaccine design and testing

T. M. Allen, B. R. Mothé, J. Sidney, P. Jing, J. L. Dzuris, M. E. Liebl, T. U. Vogel, D. H. O'Connor, X. Wang, M. C. Wussow, J. A. Thomson, J. D. Altman, David Watkins, A. Sette

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8+ response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8+ epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*012, a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparent Kd values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01+ macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.

Original languageEnglish
Pages (from-to)738-749
Number of pages12
JournalJournal of Virology
Volume75
Issue number2
DOIs
StatePublished - Jan 16 2001
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
major histocompatibility complex
Macaca mulatta
Major Histocompatibility Complex
epitopes
Epitopes
lymphocytes
Vaccines
peptides
Lymphocytes
vaccines
Peptides
cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
Human immunodeficiency virus
testing
HIV
Synthetic Genes
synthetic genes

ASJC Scopus subject areas

  • Immunology

Cite this

CD8+ lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule Mamu-A*01 : Implications for vaccine design and testing. / Allen, T. M.; Mothé, B. R.; Sidney, J.; Jing, P.; Dzuris, J. L.; Liebl, M. E.; Vogel, T. U.; O'Connor, D. H.; Wang, X.; Wussow, M. C.; Thomson, J. A.; Altman, J. D.; Watkins, David; Sette, A.

In: Journal of Virology, Vol. 75, No. 2, 16.01.2001, p. 738-749.

Research output: Contribution to journalArticle

Allen, T. M. ; Mothé, B. R. ; Sidney, J. ; Jing, P. ; Dzuris, J. L. ; Liebl, M. E. ; Vogel, T. U. ; O'Connor, D. H. ; Wang, X. ; Wussow, M. C. ; Thomson, J. A. ; Altman, J. D. ; Watkins, David ; Sette, A. / CD8+ lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule Mamu-A*01 : Implications for vaccine design and testing. In: Journal of Virology. 2001 ; Vol. 75, No. 2. pp. 738-749.
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AU - Dzuris, J. L.

AU - Liebl, M. E.

AU - Vogel, T. U.

AU - O'Connor, D. H.

AU - Wang, X.

AU - Wussow, M. C.

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