Expression of endogenous peptide-major histocompatibility complex class II complexes derived from invariant chain-antigen fusion proteins

Sarah Sanderson, Kenneth Frauwirth, Nilabh Shastri

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CD4+ T cells recognize major histocompatibility complex (MHC) class II- bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that endogenously synthesized ovalbumin or hen egg lysozyme can be efficiently presented as peptide-MHC class II complexes when they are expressed as fusion proteins with the invariant chain (Ii). Similar to the wild-type Ii, the Ii-antigen fusion proteins were associated intracellularly with MHC molecules. Most efficient 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 suggest that signals within the Ii can allow endogenously synthesized proteins to efficiently enter the MHC class II presentation pathway. They also suggest a strategy far identifying unknown antigens presented by MHC class II molecules.

Original languageEnglish (US)
Pages (from-to)7217-7221
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Aug 1 1995


ASJC Scopus subject areas

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