Immunodominance: intramolecular competition between T cell epitopes.
We have used an approach of linking previously characterized T cell epitopes into immunologically complex synthetic peptides in order to investigate the mechanism of immunodominance. Our results show that first, cI12-26 is highly dominant following immunization with the lambda repressor (cI) protein, but is a minor epitope in the context of the cI:NP peptide. In contrast, the dominant epitope in response to the cI:NP peptide is a new junctional epitope, which is composed of sequences derived from both the cI and influenza nucleoprotein (NP) segments of the composite peptide. Second, T cell recognition of cI:NP is not significantly altered by Ag processing, based on results from glutaraldehyde-fixed APC. Third, the relative affinities of cI and cI:NP for MHC binding are similar, based on in vitro competition, excluding competition at the level of MHC binding as the determinant of immunodominance. Taken together, these results are consistent with the hypothesis that immunodominance of cI:NP is determined by peptide conformation, which affects the configuration of peptide binding to MHC, thus altering T cell recognition. In conclusion, immunodominance is not simply a function of the primary amino acid sequence, but is a function of the context of the epitope within the protein molecule.
Perkins
D L
DL
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA.
Berriz
G
G
Kamradt
T
T
Smith
J A
JA
Gefter
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D010582:Bacteriophage lambda / Q000276:immunology; D004268:DNA-Binding Proteins; D000939:Epitopes; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009975:Orthomyxoviridae / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D000939:Epitopes; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D012097:Repressor Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins