THE RELATIONSHIP BETWEEN CLASS-I FINDING AFFINITY AND IMMUNOGENICITY OF POTENTIAL CYTOTOXIC T-CELL EPITOPES

The relationship between binding affinity for HLA class I molecules an d immunogenicity of discrete peptide epitopes has been analyzed in two different experimental approaches. In the first approach, the immunog enicity of potential epitopes ranging in MHC binding affinity over a 1 0,000-fold range was analyzed in HLA-A0201 transgenic mice. In the se cond approach, the antigenicity of approximately 100 different hepatit is B virus (HBV)derived potential epitopes, all carrying A0201 bindin g motifs, was assessed by using PBL of acute hepatitis patients. In bo th 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 w ith class I binding affinity measurements of either naturally processe d peptides or previously described T cell epitopes. Taken together, th ese data have important implications for the selection of epitopes for peptide-based vaccines, and also formally demonstrate the crucial rol e of determinant selection in the shaping of T cell responses. Because in most (but not all) cases, high affinity peptides seem to be immuno genic, our data also suggest that holes in the functional T cell reper toire, if they exist, may be relatively rare.