Interference of Distinct Invariant Chain Regions with Superantigen Contact Area and Antigenic Peptide Binding Groove of HLA-DR

In the endoplasmic reticulum, MHC class II ab dimers associate with the trimeric invariant chain (li), generating a nine-subunit(abli)3 complex. In the presence of li, the peptide binding groove is blocked, so that loading with self or antigenic peptides can only occur after proteolytic removal of li in specialized post-Golgi compartments. The class 11-associated invariant chain peptide region of li (about residues 81-1 04) is known to mediate binding to class II molecules and blockade of the groove, but this does not exclude additional contact sites for li. Using a set of overlapping li peptides and recombinant soluble li, we demonstrate here that a large segment of Ii encompassing approximately residues 71 to 128 interacts with HLA-DR molecules. The N- and C-terminal regions of this Ii segment appear to bind outside the peptide groove to the contact area for the staphylococcal superantigen Staphylococcus aureus enterotoxin B on the a1 domain. The core region of this segment (residues 95-108)prevents binding of antigenic peptides, probably by interaction with the peptide groove. Occupation of the groove with antigenic peptides abolishes binding not only of the core region, but also that of those Ii peptides that bind outside the groove. These findings suggest the existence of distinct conformational states of class II molecules, with Ii binding preferentially to one form

Business Model Innovation vs. Business Model Inertia: the Role of Disruptive Technologies

This contribution addresses the impact of disruptive technologies on business model innovation. While such technologies have the potential to significantly alter the way in which businesses operate, business model inertia hinders companies from adopting the new technological possibilities. Little research has focused on the difficulties incumbents face when innovating their business models. By reviewing current literature on business model innovation, this paper summarizes challenges companies face when dealing with potential disruptive technologies and creating viable business models

Interference of distinct invariant chain regions with superantigen contact area and antigenic peptide binding groove of HLA-DR.

Abstract In the endoplasmic reticulum, MHC class II alpha beta dimers associate with the trimeric invariant chain (li), generating a nine-subunit (alpha beta li)3 complex. In the presence of li, the peptide binding groove is blocked, so that loading with self or antigenic peptides can only occur after proteolytic removal of li in specialized post-Golgi compartments. The class II-associated invariant chain peptide region of li (about residues 81-104) is known to mediate binding to class II molecules and blockade of the groove, but this does not exclude additional contact sites for li. Using a set of overlapping li peptides and recombinant soluble li, we demonstrate here that a large segment of li encompassing approximately residues 71 to 128 interacts with HLA-DR molecules. The N- and C-terminal regions of this li segment appear to bind outside the peptide groove to the contact area for the staphylococcal superantigen Staphylococcus aureus enterotoxin B on the alpha 1 domain. The core region of this segment (residues 95-108) prevents binding of antigenic peptides, probably by interaction with the peptide groove. Occupation of the groove with antigenic peptides abolishes binding not only of the core region, but also that of those li peptides that bind outside the groove. These findings suggest the existence of distinct conformational states of class II molecules, with li binding preferentially to one form.</jats:p