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 10-50 times baseline levels, the presentation of synthetic antigenic peptides to murine T cell hybridomas, by an exchange mechanism at cell surface MHC class II molecules. Two differing activities, to promote the release of antigenic peptide in the presence or absence in solution of a second antigenic peptide, were characterized with truncation homologs through assays for release 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 *peptide to 'empty' DR1. Peptides such as Ii81-88, LPKSAKPV, released prebound hMBP *peptide from DR1 without free hMBP peptide in solution. They also exchanged hMBP *peptide from solution for prebound hMBP peptide. Peptides including hIi77-83, LRMKLPK, released hMBP *peptide only when free hMBP peptide 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 *peptide or several *Ii-Key truncation homologs, with respective not biotinylated forms, demonstrated that the Ii77-83, LRMKLPK, binding site was distinct from the HLA-DR1 antigenic peptide binding site.
Xu
M
M
Antigen Express, Inc., Worcester, MA, USA. antigenexp@aol.com
Jackson
R
R
Adams
S
S
Humphreys
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D019921:Biotinylation; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015798:HLA-DR1 Antigen / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; C045084:invariant chain