Epitopes described in "The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes."

Article Authors:A Sette; A Vitiello; B Reherman; P Fowler; R Nayersina; W M Kast; C J Melief; C Oseroff; L Yuan; J Ruppert; J Sidney; M F del Guercio; S Southwood; R T Kubo; R W Chesnut; H M Grey; F V Chisari
Article Title:The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes.
Reference Detail
Reference ID:200025
Abstract:The relationship between binding affinity for HLA class I molecules and immunogenicity of discrete peptide epitopes has been analyzed in two different experimental approaches. In the first approach, the immunogenicity of potential epitopes ranging in MHC binding affinity over a 10,000-fold range was analyzed in HLA-A*0201 transgenic mice. In the second approach, the antigenicity of approximately 100 different hepatitis B virus (HBV)-derived potential epitopes, all carrying A*0201 binding motifs, was assessed by using PBL of acute hepatitis patients. In both cases, it was found that an affinity threshold of approximately 500 nM (preferably 50 nM or less) apparently determines the capacity of a peptide epitope to elicit a CTL response. These data correlate well with class I binding affinity measurements of either naturally processed peptides or previously described T cell epitopes. Taken together, these data have important implications for the selection of epitopes for peptide-based vaccines, and also formally demonstrate the crucial role of determinant selection in the shaping of T cell responses. Because in most (but not all) cases, high affinity peptides seem to be immunogenic, our data also suggest that holes in the functional T cell repertoire, if they exist, may be relatively rare.
Affiliations:Cytel, San Diego, CA 92121, USA.
Reference Type:Literature
PubMed ID:7527444
Journal:J Immunol
Journal Volume:153
Article Pages:5586-92
Journal ISSN:0022-1767
Article Chemical List:Epitopes;HLA-A Antigens;Hepatitis B Antigens;Peptides
Article MeSH List:Amino Acid Sequence; Animals; Cell Line; Cytotoxicity Tests, Immunologic; Epitopes(immunology); HLA-A Antigens(immunology); Hepatitis B(immunology); Hepatitis B Antigens(immunology); Humans; Mice; Mice, Transgenic; Molecular Sequence Data; Peptides(immunology); Protein Binding(immunology); T-Lymphocytes, Cytotoxic(immunology)
Curation Last Updated:2015-07-30 20:03:51