Processing of exogenous hepatitis B surface antigen particles for Ld-restricted epitope presentation depends on exogenous beta2-microglobulin.

Processing of exogenous hepatitis B surface antigen (HBsAg) particles in an endolysosomal compartment generates peptides that bind to the major histocompatibility complex (MHC) class I molecule Ld and are presented to CD8+ cytotoxic T lymphocytes. Surface-associated 'empty' MHC class I molecules associated neither with peptide, nor with beta2-microglobulin (beta2m) are involved in this alternative processing pathway of exogenous antigen for MHC class I-restricted peptide presentation. Here, we demonstrate that internalization of exogenous beta2m is required for endolysosomal generation of presentation-competent, trimeric Ld molecules in cells pulsed with exogenous HBsAg. These data point to a role of endocytosed exogenous beta2m in the endolysosomal assembly of MHC class I molecules that present peptides from endosomally processed, exogenous antigen.