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Mutations in a dominant Nef epitope of simian immunodeficiency virus diminish TCR:epitope peptide affinity but not epitope peptide:MHC class I binding.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Sep 15; Vol. 187 (6), pp. 3300-13. Date of Electronic Publication: 2011 Aug 12. - Publication Year :
- 2011
-
Abstract
- Viruses like HIV and SIV escape from containment by CD8(+) T lymphocytes through generating mutations that interfere with epitope peptide:MHC class I binding. However, mutations in some viral epitopes are selected for that have no impact on this binding. We explored the mechanism underlying the evolution of such epitopes by studying CD8(+) T lymphocyte recognition of a dominant Nef epitope of SIVmac251 in infected Mamu-A*02(+) rhesus monkeys. Clonal analysis of the p199RY-specific CD8(+) T lymphocyte repertoire in these monkeys indicated that identical T cell clones were capable of recognizing wild-type (WT) and mutant epitope sequences. However, we found that the functional avidity of these CD8(+) T lymphocytes for the mutant peptide:Mamu-A*02 complex was diminished. Using surface plasmon resonance to measure the binding affinity of the p199RY-specific TCR repertoire for WT and mutant p199RY peptide:Mamu-A*02 monomeric complexes, we found that the mutant p199RY peptide:Mamu-A*02 complexes had a lower affinity for TCRs purified from CD8(+) T lymphocytes than did the WT p199RY peptide:Mamu-A*02 complexes. These studies demonstrated that differences in TCR affinity for peptide:MHC class I ligands can alter functional p199RY-specific CD8(+) T lymphocyte responses to mutated epitopes, decreasing the capacity of these cells to contain SIVmac251 replication.
- Subjects :
- Animals
Base Sequence
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Epitopes, T-Lymphocyte immunology
Epitopes, T-Lymphocyte metabolism
Gene Products, nef immunology
Gene Products, nef metabolism
Immune Evasion genetics
Immune Evasion immunology
Immunodominant Epitopes genetics
Immunodominant Epitopes immunology
Macaca mulatta
Molecular Sequence Data
Protein Binding genetics
Protein Binding immunology
Receptors, Antigen, T-Cell genetics
Receptors, Antigen, T-Cell immunology
Reverse Transcriptase Polymerase Chain Reaction
Simian Immunodeficiency Virus immunology
Simian Immunodeficiency Virus metabolism
Epitopes immunology
Epitopes, T-Lymphocyte genetics
Gene Products, nef genetics
Histocompatibility Antigens Class I metabolism
Mutation
Receptors, Antigen, T-Cell metabolism
Simian Immunodeficiency Virus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 187
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21841125
- Full Text :
- https://doi.org/10.4049/jimmunol.1101080