DIFFERENCES AND SIMILARITIES IN THE A2.1-RESTRICTED CYTOTOXIC T-CELL REPERTOIRE IN HUMANS AND HUMAN-LEUKOCYTE ANTIGEN-TRANSGENIC MICE

HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity wi th human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA-A2. 1/K-b transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the level of overlap between the A2 .1-restricted CTL repertoire of A2.1/K-b-transgenic mice and A2.1(+) h umans. In both humans and mice, a major histocompatibility complex aff inity threshold of approximately 500 nM appears to determine the capac ity of a peptide to elicit a CTL response. Good concordance between th e human data in vitro and mouse data in vivo was observed with 85% of the high-binding peptides, 58% of the intermediate binders, and 83% of the low/negative binders. Although some peptides immunogenic for mous e CTL but not for humans (and vice versa) could be identified, the dat a as a whole suggest an extensive overlap between T cell receptor repe rtoires of mouse and human CTL and support the use of HLA-transgenic m ice for the identification of potential human CTL epitopes.