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
Autor: | J, Sidney, J L, Dzuris, M J, Newman, R P, Johnson, A, Kaur, K, Amitinder, C M, Walker, E, Appella, B, Mothe, D I, Watkins, A, Sette |
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Rok vydání: | 2000 |
Předmět: |
Immunology
Epitopes T-Lymphocyte Peptide binding Biology Ligands Protein Engineering medicine.disease_cause Peptide Mapping Epitope Immediate-Early Proteins medicine Animals Immunology and Allergy Viral Regulatory and Accessory Proteins Amino Acids Genetics Binding Sites Ligand C-terminus Histocompatibility Antigens Class I Wild type Protein engineering Simian immunodeficiency virus Macaca mulatta Peptide Fragments Amino Acid Substitution Peptide binding motif Biochemistry Simian Immunodeficiency Virus Oligopeptides Algorithms Protein Binding |
Zdroj: | The Journal of Immunology. 165:6387-6399 |
ISSN: | 1550-6606 0022-1767 |
Popis: | 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. |
Databáze: | OpenAIRE |
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