Peptide-priming of cytolytic T cell immunity in vivo using beta 2-microglobulin as an adjuvant.
CTL recognize oligopeptides bound to MHC class I molecules. Immunization of animals with antigenic peptides has often failed to stimulate CTL responses. We confirm that immunizations with several peptides, including natural and optimally active antigenic sequences, do not prime cytotoxic immunity in mice. However, immunization with peptides together with human beta 2-microglobulin primes Ag-specific CTL. Priming is observed when animals receive injections either i.v. with ex vivo peptide/beta 2-microglobulin-pulsed cells or s.c. with an admixture of peptide and beta 2-microglobulin. beta 2-Microglobulin promotes the priming of CTL immunity if it is added with peptide, but not if it is added after cells are exposed to peptide. Synthetic peptides and mixtures of peptides from enzymatically cleaved Ag are immunogenic. When a tryptic digest of OVA or the synthetic peptide (OVA258-276) are used as immunogens, the CTL that respond recognize the endogenously processed epitope presented by an OVA-transfected target cell. The peptide + beta 2-microglobulin-primed CTL are CD4-CD8+ and are class I MHC restricted. Using the immunization protocol with beta 2-microglobulin, we have primed CTL responses with peptides from OVA, Sendai virus, and vesicular stomatitis virus. These results may explain previous failures to prime CTL with peptides in vivo and provide a novel approach for developing peptide-based vaccines for viral diseases.
Division of Lymphocyte Biology, Dana Farber Cancer Institute, Boston, MA 02115.
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D000276:Adjuvants, Immunologic; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D001613:beta 2-Microglobulin / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D001613:beta 2-Microglobulin; D010047:Ovalbumin