Alternative processing of endogenous or exogenous antigens extends the immunogenic, H-2 class I-restricted peptide repertoire.
We investigated the murine, MHC class I-restricted cytotoxic T lymphocyte (CTL) response to a viral antigen delivered by different vaccination strategies to either the endogenous, or an alternative exogenous processing pathway. The immunization techniques used primed distinct (though overlapping) repertoires of CTL epitopes. In vitro studies revealed evidence for the generation of immunogenic, L(d)- and K(b)-binding peptides from endocytosed, exogenous antigen by alternative (endolysosomal) processing. Endogenous antigens expressed by DNA vaccines as a stress protein-associated fusion proteins gains access from the cytosol to endolysosomal processing. Hence, exogenous as well as endogenous protein antigens can gain access to alternative processing pathways and can give rise to an extended repertoire of antigenic epitopes. These studies indicate novel ways for the rational design of vaccine candidates that can prime CTL responses.
Schirmbeck
Reinhold
R
Institute of Medical Microbiology and Immunology, University of Ulm, Helmholtzstr 8/1, Albert Einstein Allee 11, D-89081, Ulm, Germany.
Reimann
Jörg
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D002352:Carrier Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D001613:beta 2-Microglobulin / Q000502:physiology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006514:Hepatitis B Surface Antigens; C073119:TAP1 protein, human; D019444:Vaccines, DNA; D001613:beta 2-Microglobulin