Identification of residues in the class II-associated Ii peptide (CLIP) region of invariant chain that affect efficiency of MHC class II-mediated antigen presentation in an allele-dependent manner

Abstract

Invariant chain (Ii) associates with class II MHC molecules and is crucial for Ag presentation by class II molecules. A general explanation for how invariant chain (Ii) associates with polymorphic MHC class II molecules has been suggested by the crystallographic structure of CLIP (class Il-associated Ii peptide) complexed with an HLA class II molecule, HLA-DR3. We show here that methionine residues at positions 93 and 99 in Ii are important in MHC class 11-media ted Ag presentation, but function in an allele-dependent manner. Introduction of a Met→Ala mutation at position 99 in Ii (M99Ali) impaired presentation of peptides derived from exogenous proteins by I-A d and I-A u class II molecules..