INVARIANT CHAIN MADE IN ESCHERICHIA COLI HAS AN EXPOSED N-TERMINAL SEGMENT THAT BLOCKS ANTIGEN BINDING TO HLA-DR1 AND A TRIMERIC C-TERMINAL SEGMENT THAT BINDS EMPTY HLA-DR1

摘要

Invariant chain (Ii), a membrane glycoprotein, binds class II major histocompatibility complex (MHC) glycoproteins, probably via its class II-associated Ii peptide (CLIP) segment, and escorts them toward antigen-containing endosomal compartments, We find that a soluble, trimeric ectodomain of Ii expressed and purified from Escherichia coli blocks peptide binding to soluble HLA-DR1. Proteolysis indicates that Ii contains two structural domains, The C-terminal two-thirds forms an alpha-helical domain that trimerizes and interacts with empty HLA-DR1 molecules, augmenting rather than blocking peptide binding, The N-terminal one-third, which inhibits peptide binding, is proteolytically susceptible over its entire length, In the trimer, the N-terminal domains act independently,vith each CLIP segment exposed and free to bind an MHC class II molecule, while the C-terminal domains act as a trimeric unit. [References: 41]