CTL RESPONSES OF HLA-A2.1-TRANSGENIC MICE SPECIFIC FOR HEPATITIS-C VIRAL PEPTIDES PREDICT EPITOPES FOR CTL OF HUMANS CARRYING HLA-A2.1

Vaccine development in animal models depends on ability to recognize e pitopes seen by human T cells. In this work, we show that CTL response s in transgenic mice expressing human HLA-A2.1 prospectively predict t he same four of 11 hepatitis C virus (HCV) structural protein-derived peptides, expressing a sequence motif for HLA-A2.1 binding, that are a ctually recognized by human A2.1-restricted CTLs. The CTLs also recogn ized targets endogenously expressing these proteins. Human CTLs from H CV-infected patients, tested by using the same peptides, revealed a vi rtually identical response repertoire. A highly conserved HCV core pep tide was the most immunogenic, and may be a valuable component of a va ccine against a broad range of HCV isolates in HLA-A2-positive patient s. These results suggest that, in spite of species differences, the T cell repertoire is plastic enough to allow a similar response when the same class I MHC molecule is presenting the peptide. Thus, the HLA mo lecule plays the primary role in determining which peptides are recogn ized by CTLs. This transgenic mouse model is important for the study o f HLA-restricted CTL determinants and for an approach to design a pote ntial HCV vaccine.