Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice: Dependence on HLA class II restricted T-H response

CTL play a pivotal role in the immune response during viral infections. In this study, the HLA class II restricted T-H requirement for optimal in vivo induction of HLA class I restricted CTL responses has been investigated. T owards this goal, transgenic mice expressing both HLA class I (A*0201 or A2 .1) and class II (DRB1*0101 or DR1) molecules have been derived. Immunizati on of these mice with an HLA A*0201-restricted and CMV-specific CTL epitope (pp65(495-503)), and either of three different tetanus toxin-derived MHC c lass II-binding TH epitopes, resulted in a vigorous Cn response. CTL specif ic for the pp65(495-503) epitope were dramatically enhanced in mice express ing both the HLA-DR1 and HLA-A*0201 transgenes. Notably, preinjection of th ree TT peptides (TT639-652, TT830-843, and TT947-967) increased the capabil ity of HLA A*0201/DR1 Tg mice to respond to subsequent immunization with th e T-H + CTL peptide mixture. These results indicate that the use of HLA A*0 201/DR1 Tg mice constitute a versatile model system (in lieu of immunizing humans) for the study of both HLA class I and class II restricted T-cell re sponses. These studies provide a rational model for the design and assessme nt of new minimal-epitope vaccines based on their in vivo induction of a pa thogen-specific CTL response. Human Immunology 61, 764-779 (2000). (C) Amer ican Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.