Binding affinity independent contribution of peptide length to the stability of peptide-HLA-DR complexes in live antigen presenting cells

The effect of peptide length on the stability of peptide-HLR-DR1 (DR1) complexes was analyzed using two peptide series of increasing length, each containing a 7mer core with five DR1-binding anchors, extended stepwise with A1a residues at the N- and C-terminus, respectively. The A1a extensions, although did not affect binding affinity, significantly increased the half lives of peptide-DR1 complexes (from 1.5 h up to 10 h) in live antigen presenting cells (APC). Flanking residues from position −2 to 0 and 8 to 11 were involved in the affinity-independent increase of complex stability. The shortest (8mer and 9mer) peptides, with in vivo half lives of 9 residues, and the longevity of complexes seems to depend on full of occupation of the binding site.