In vivo enhancement of peptide display by MHC class II molecules with small molecule catalysts of peptide exchange.
Melissa J Call, Xuechao Xing, Gregory D Cuny, Nilufer P Seth, Daniel M Altmann, Lars Fugger, Michelle Krogsgaard, Ross L Stein, Kai W Wucherpfennig
J Immunol | Published : 2009
Rapid binding of peptides to MHC class II molecules is normally limited to a deep endosomal compartment where the coordinate action of low pH and HLA-DM displaces the invariant chain remnant CLIP or other peptides from the binding site. Exogenously added peptides are subject to proteolytic degradation for extended periods of time before they reach the relevant endosomal compartment, which limits the efficacy of peptide-based vaccines and therapeutics. In this study, we describe a family of small molecules that substantially accelerate the rate of peptide binding to HLA-DR molecules in the absence of HLA-DM. A structure-activity relationship study resulted in analogs with significantly higher..View full abstract