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Comparison of cytotoxic T lymphocyte responses induced by peptide or DNA immunization: implications on immunogenicity and immunodominance.
- Source :
-
European journal of immunology [Eur J Immunol] 1997 Mar; Vol. 27 (3), pp. 671-8. - Publication Year :
- 1997
-
Abstract
- To study the mechanisms that influence the immunogenicity and immunodominance of potential cytotoxic T lymphocyte (CTL) epitopes, we conducted a systematic analysis of the CTL response raised in HLA-A*0201/Kb (A2/Kb) transgenic mice against the viral antigen, hepatitis B virus polymerase (HBV pol). From a pool of 26 nonamer peptides containing the HLA-A*0201-binding motif, we selected A2-binding peptides, immunized A2/Kb animals, and tested the CTL raised against the peptide for recognition of HBV pol transfectants. Of nine immunogenic CTL epitopes, only four were recognized on HBV pol transfectants, whereas the other five were cryptic. Characterization of the peptide-specific CTL lines indicated that crypticity may result from either poor processing or low T cell receptor (TCR) avidity. To identify the immunodominant epitopes, we determined the CTL specificities induced in A2/Kb animals in response to priming with HBV pol cDNA. We obtained a response against three epitopes that were contained with the set of four epitopes recognized by peptide-specific CTL on HBV pol transfectants. Comparative analysis of cDNA priming and peptide priming revealed, therefore, the presence of a subdominant epitope. We conclude that for the HBV pol antigen, the repertoire of CTL specificities is shaped by major histocompatibility complex class I peptide binding capacity, antigen processing, and TCR availability.
- Subjects :
- Amino Acid Sequence
Animals
Epitope Mapping
Genes, pol
HLA Antigens immunology
Hepatitis B virus enzymology
Humans
Mice
Mice, Transgenic
Receptors, Antigen, T-Cell immunology
DNA, Viral immunology
DNA-Directed DNA Polymerase immunology
Hepatitis B Antigens immunology
Hepatitis B virus immunology
Peptides immunology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 27
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 9079808
- Full Text :
- https://doi.org/10.1002/eji.1830270315