EXPRESSION OF ENDOGENOUS PEPTIDE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II COMPLEXES DERIVED FROM INVARIANT CHAIN-ANTIGEN FUSION PROTEINS

CD4(+) T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sourc es. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II p resentation pathway. We show here that endogenously synthesized ovalbu min or hen egg lysozyme can be efficiently presented as peptide-MHC cl ass II complexes when they are expressed as fusion proteins with the i nvariant chain (Ii). Similar to the wild-type Ii, the Ii-antigen fusio n proteins were associated intracellularly with MHC molecules, Most ef ficient expression of endogenous peptide-MHC complex was obtained with fusion proteins that contained the endosomal targeting signal within the N-terminal cytoplasmic Ii residues but did not require the luminal residues of Ii that are known to bind MHC molecules. These results su ggest that signals within the Ii can allow endogenously synthesized pr oteins to efficiently enter the MHC class II presentation pathway. The y also suggest a strategy for identifying unknown antigens presented b y MHC class II molecules.