Similar as well as distinct MHC class I‐binding peptides are generated by exogenous and endogenous processing of hepatitis B virus surface antigen

Murine MHC class I‐restricted cytotoxic T lymphocyte (CTL) responses can be primed by exogenous as well as endogenous hepatitis B surface antigen (HBsAg). Immunodominant CTL‐defined epitopes of this viral envelope protein are the Ld ‐binding 12‐mer S28 – 39 peptide IPQSLDSWWTSL in H‐2 d mice, and the Kb ‐binding 8‐mer S208 – 215 peptide ILSPFLPL in H‐2b mice. We tested if CTL recognizing these epitopes can be primed in vivo by HBsAg delivered as either an exogenous antigen (native HBsAg lipoprotein particles), or an endogenous antigen (plasmid DNA encoding HBsAg). Primed T cells were restimulated in vitro prior to the cytotoxicity assay with cells presenting the H‐2 class I‐binding epitopes generated by either exogenous or endogenous processing of HBsAg. The data indicate that the Ld ‐binding peptide S28 – 39 is generated during exogenous as well as endogenous processing of HBsAg. In contrast, the Kb ‐binding peptide S208 – 215 is generated during exogenous but not endogenous processing of HBsAg. Hence, some but not all MHC class I‐binding, immunogenic peptides are generated during endogenous and exogenous processing of HBsAg but there also exists a repertoire of immunogenic peptides of viral origin that is only revealed after exogenous processing of viral proteins.