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.