Dendritic cells pulsed with exogenous hepatitis B surface antigen particles efficiently present epitopes to MHC class I-restricted cytotoxic T cells.

L(d)- and K(b)-binding epitopes processed by murine dendritic cells (DC) pulsed with exogenous, particulate hepatitis B surface antigen (HBsAg) are presented to cytotoxic T lymphocytes (CTL). The specific and dose-dependent induction of IFN-gamma release and cytotoxicity in CTL by metabolically active DC did not depend on antigenic peptides contaminating the particles, was cytochalasin D resistant, independent of the maturation state of DC, and blocked by primaquine, amiloride and NH(4)Cl (indicating involvement of acid proteolysis). The specific immunostimulatory phenotype of pulsed DC was maintained for about 3 h after the end of the pulse but rapidly decayed thereafter. Processing of L(d)- and K(b)-binding epitopes from exogenous HBsAg particles by pulsed DC for presentation was TAP independent. Surface-associated 'empty' (presentation-deficient) 64(+) L(d) molecules (defined by the mAb 64-3-7), but not trimeric (presentation-competent) 30(+) L(d) molecules (defined by the mAb 30-5-7) had to be available during the pulse of DC with exogenous HBsAg particles to generate 30(+) L(d)molecules that present the antigenic S(28-39) peptide. Exogenous beta2-microglobulin present during the pulse of DC with HBsAg particles facilitated presentation of L(d)- and K(b)-restricted epitopes. DC generated from bone marrow progenitors in vitro, as well as splenic and liver DC (generated in vivo) presented epitopes to specific CTL. HBsAg particles thus efficiently enter an alternative processing pathway in DC that leads to presentation of epitopes to MHC class I-restricted CTL.