Studies on activities of invariant chain peptides on releasing or exchanging of antigenic peptides at human leukocyte antigen-DR1

An invariant chain peptide (Ii77-92; YRMKLPKSAKPVSQMR; 'Ii-Key') enhances 1 0-50 times baseline levels, the presentation of synthetic antigenic peptide s to murine T cell hybridomas, by an exchange mechanism at cell surface MHC class II molecules. Two differing activities, to promote the release of an tigenic peptide in the presence or absence in solution of a second antigeni c peptide, were characterized with truncation homologs through assays for r elease or binding of human myelin basic protein biotinylated (*) peptide 90 -102 on purified HLA-DR1: 1) release of bound hMBP *peptide from DR1 in the presence or absence of free hMBP peptide in solution, 2) exchange of hMBP *peptide from solution with hMBP peptide on DR1, and 3) binding of hMBP *pe ptide to 'empty' DR1. Peptides such as Ii81-88, LPKSAKPV, released prebound hMBP *peptide from DR1 without free hMBP peptide in solution. They also ex changed hMBP *peptide from solution for prebound hMBP peptide. Peptides inc luding hIi77-83, LRMKLPK, released hMBP *peptide only when free hMBP peptid e was in solution. Nevertheless, hIi77-85,LRMKLPKPP, released hMBP peptide without hMBP peptide in solution. Either type of peptide accelerated hMBP * peptide binding to 'empty' DR1. Competitive binding assays with hMBP *pepti de or several *Ii-Key truncation homologs, with respective not biotinylated forms, demonstrated that the Ii77-83, LRMKLPK, binding site was distinct f rom the HLA-DR1 antigenic peptide binding site.