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 7 mer core with five DR1-binding anchors, extended stepwise with Ala residues at the N- and C-terminus, respectively. The Ala extensions, although did not affect binding affinity, significant ly 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 (8 mer and 9 mer) peptide s, with in vivo half lives of <2.5 h, were unable to form stable compl exes with DR1 in presence of HLA-DM (DM) molecules, and were poor comp etitors of antigen presentation. Longer peptides were resistant to DM- mediated unloading, and were efficient competitors of antigen presenta tion. Thus, DM appears to limit short peptides in establishing biologi cally relevant DR occupancy, despite their high binding affinity. In A PC, stable complexes can form only with high affinity peptides of >9 r esidues, and the longevity of complexes seems to depend on full of occ upation of the binding site. Human Immunology 59, 463-471 (1998). (C) American Society for Histocompatibility and Immunogenetics, 1998. Publ ished by Elsevier Science Inc.