Identification of the lateral interaction surfaces of human histocompatibility leukocyte antigen (HLA)-DM with HLA-DR1 by formation of tethered complexes that present enhanced HLA-DM catalysis.

ABSTRACT: Human histocompatibility leukocyte antigen (HLA)-DM is a major histocompatibility complex (MHC)-like protein that catalyzes exchange of antigenic peptides from MHC class II molecules. To investigate the molecular details of this catalysis we created four covalent complexes between HLA-DM and the MHC class II allele DR1. We introduced a disulfide bond between the naturally occurring cysteine beta46 on HLA-DM and an engineered cysteine on the end of a linker attached to either the NH(2)- or the COOH terminus of an antigenic peptide that is tightly bound on DR1. We find that when DM is attached to the NH(2) terminus of the peptide, it can, for all linker lengths tested, catalyze exchange of the peptide with a half-life a few minutes (compared with uncatalyzed t(1/2) > 100 h). This rate, which

SUBMITTER: Stratikos E 

PROVIDER: S-EPMC2193930 | biostudies-literature | 2002 Jul

REPOSITORIES: biostudies-literature