Definition of the Mamu A*01 peptide binding specificity: Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins

J. Sidney, J. L. Dzuris, M. J. Newman, R. P. Johnson, K. Amitinder, C. M. Walker, E. Appella, B. Mothe, David Watkins, A. Sette

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Single amino acid substitution analogs of the known Mamu A*01 binding peptide gag 181-190 and libraries of naturally occurring sequences of viral or bacterial origin were used to rigorously define the peptide binding motif associated with Mamu A*01 molecules. The presence of S or T in position 2, P in position 3, and hydrophobic or aromatic residues at the C terminus is associated with optimal binding capacity. At each of these positions, additional residues are also tolerated but associated with significant decreases in binding capacity. The presence of at least two preferred and one tolerated residues at the three anchor positions is necessary for good Mamu A*01 binding; optimal ligand size is 8-9 residues. This detailed motif has been used to map potential epitopes from SIVmac239 regulatory proteins and to engineer peptides with increased binding capacity. A total of 13 wild type and 17 analog candidate epitopes were identified. Furthermore, our analysis reveals a significantly lower than expected frequency of epitopes in early regulatory proteins, suggesting a possible evolutionary- and/or immunoselection directed against variants of viral products that contain CTL epitopes.

Original languageEnglish
Pages (from-to)6387-6399
Number of pages13
JournalJournal of Immunology
Volume165
Issue number11
StatePublished - Dec 1 2000
Externally publishedYes

Fingerprint

Simian Immunodeficiency Virus
Epitopes
Ligands
Peptides
Proteins
Amino Acid Substitution
Libraries

ASJC Scopus subject areas

  • Immunology

Cite this

Sidney, J., Dzuris, J. L., Newman, M. J., Johnson, R. P., Amitinder, K., Walker, C. M., ... Sette, A. (2000). Definition of the Mamu A*01 peptide binding specificity: Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins. Journal of Immunology, 165(11), 6387-6399.

Definition of the Mamu A*01 peptide binding specificity : Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins. / Sidney, J.; Dzuris, J. L.; Newman, M. J.; Johnson, R. P.; Amitinder, K.; Walker, C. M.; Appella, E.; Mothe, B.; Watkins, David; Sette, A.

In: Journal of Immunology, Vol. 165, No. 11, 01.12.2000, p. 6387-6399.

Research output: Contribution to journalArticle

Sidney, J, Dzuris, JL, Newman, MJ, Johnson, RP, Amitinder, K, Walker, CM, Appella, E, Mothe, B, Watkins, D & Sette, A 2000, 'Definition of the Mamu A*01 peptide binding specificity: Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins', Journal of Immunology, vol. 165, no. 11, pp. 6387-6399.
Sidney, J. ; Dzuris, J. L. ; Newman, M. J. ; Johnson, R. P. ; Amitinder, K. ; Walker, C. M. ; Appella, E. ; Mothe, B. ; Watkins, David ; Sette, A. / Definition of the Mamu A*01 peptide binding specificity : Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins. In: Journal of Immunology. 2000 ; Vol. 165, No. 11. pp. 6387-6399.
@article{deba72f861904d24a203e1dd61f946f9,
title = "Definition of the Mamu A*01 peptide binding specificity: Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins",
abstract = "Single amino acid substitution analogs of the known Mamu A*01 binding peptide gag 181-190 and libraries of naturally occurring sequences of viral or bacterial origin were used to rigorously define the peptide binding motif associated with Mamu A*01 molecules. The presence of S or T in position 2, P in position 3, and hydrophobic or aromatic residues at the C terminus is associated with optimal binding capacity. At each of these positions, additional residues are also tolerated but associated with significant decreases in binding capacity. The presence of at least two preferred and one tolerated residues at the three anchor positions is necessary for good Mamu A*01 binding; optimal ligand size is 8-9 residues. This detailed motif has been used to map potential epitopes from SIVmac239 regulatory proteins and to engineer peptides with increased binding capacity. A total of 13 wild type and 17 analog candidate epitopes were identified. Furthermore, our analysis reveals a significantly lower than expected frequency of epitopes in early regulatory proteins, suggesting a possible evolutionary- and/or immunoselection directed against variants of viral products that contain CTL epitopes.",
author = "J. Sidney and Dzuris, {J. L.} and Newman, {M. J.} and Johnson, {R. P.} and K. Amitinder and Walker, {C. M.} and E. Appella and B. Mothe and David Watkins and A. Sette",
year = "2000",
month = "12",
day = "1",
language = "English",
volume = "165",
pages = "6387--6399",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Definition of the Mamu A*01 peptide binding specificity

T2 - Application to the identification of wild-type and optimized ligands from simian immunodeficiency virus regulatory proteins

AU - Sidney, J.

AU - Dzuris, J. L.

AU - Newman, M. J.

AU - Johnson, R. P.

AU - Amitinder, K.

AU - Walker, C. M.

AU - Appella, E.

AU - Mothe, B.

AU - Watkins, David

AU - Sette, A.

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Single amino acid substitution analogs of the known Mamu A*01 binding peptide gag 181-190 and libraries of naturally occurring sequences of viral or bacterial origin were used to rigorously define the peptide binding motif associated with Mamu A*01 molecules. The presence of S or T in position 2, P in position 3, and hydrophobic or aromatic residues at the C terminus is associated with optimal binding capacity. At each of these positions, additional residues are also tolerated but associated with significant decreases in binding capacity. The presence of at least two preferred and one tolerated residues at the three anchor positions is necessary for good Mamu A*01 binding; optimal ligand size is 8-9 residues. This detailed motif has been used to map potential epitopes from SIVmac239 regulatory proteins and to engineer peptides with increased binding capacity. A total of 13 wild type and 17 analog candidate epitopes were identified. Furthermore, our analysis reveals a significantly lower than expected frequency of epitopes in early regulatory proteins, suggesting a possible evolutionary- and/or immunoselection directed against variants of viral products that contain CTL epitopes.

AB - Single amino acid substitution analogs of the known Mamu A*01 binding peptide gag 181-190 and libraries of naturally occurring sequences of viral or bacterial origin were used to rigorously define the peptide binding motif associated with Mamu A*01 molecules. The presence of S or T in position 2, P in position 3, and hydrophobic or aromatic residues at the C terminus is associated with optimal binding capacity. At each of these positions, additional residues are also tolerated but associated with significant decreases in binding capacity. The presence of at least two preferred and one tolerated residues at the three anchor positions is necessary for good Mamu A*01 binding; optimal ligand size is 8-9 residues. This detailed motif has been used to map potential epitopes from SIVmac239 regulatory proteins and to engineer peptides with increased binding capacity. A total of 13 wild type and 17 analog candidate epitopes were identified. Furthermore, our analysis reveals a significantly lower than expected frequency of epitopes in early regulatory proteins, suggesting a possible evolutionary- and/or immunoselection directed against variants of viral products that contain CTL epitopes.

UR - http://www.scopus.com/inward/record.url?scp=0034353517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034353517&partnerID=8YFLogxK

M3 - Article

C2 - 11086077

AN - SCOPUS:0034353517

VL - 165

SP - 6387

EP - 6399

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -