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. Towards 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. Immunization 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 class II-binding T(H) epitopes, resulted in a vigorous CTL response. CTL specific for the pp65(495-503) epitope were dramatically enhanced in mice expressing both the HLA-DR1 and HLA-A*0201 transgenes. Notably, preinjection of three TT peptides (TT(639-652), TT(830-843), and TT(947-967)) increased the capability of HLA A*0201/DR1 Tg mice to respond to subsequent immunization with the T(H) + CTL peptide mixture. These results indicate that the use of HLA A*0201/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 responses. These studies provide a rational model for the design and assessment of new minimal-epitope vaccines based on their in vivo induction of a pathogen-specific CTL response.
BenMohamed
L
L
Laboratory of Vaccine Research, the Department of Biostatistics, City of Hope National Medical Center, Duarte, California, USA.
Krishnan
R
R
Longmate
J
J
Auge
C
C
Low
L
L
Primus
J
J
Diamond
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010455:Peptides; D010750:Phosphoproteins; D013744:Tetanus Toxin; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; C065418:cytomegalovirus matrix protein 65kDa