Short peptide sequences mimic HLA-DM functions.
HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. It is known that DM interaction with MHC II involves conformational changes in the MHC II molecule leading to the disturbance of H-bonds formed between the bound peptide and the MHC II groove leading to peptide dissociation. The specific region of the DM molecule that induces this peptide dissociation is not defined. In this study, we describe three short peptides (helper peptides) that accelerate DM-catalyzed peptide exchange. Kinetic studies presented here demonstrate that these peptides act similarly to DM in; (a) enhancing peptide binding to HLA-DR1; (b) dissociation of complexes of peptide-DR1; and (c) maintaining a receptive conformation of empty DR1. We further report that helper peptides are effective in increasing peptide binding to DR1 expressed on B cells in vitro, and, when mixed with peptide and adjuvant, cause enhanced T cell priming in HLA-DR1 Tg mice. We suggest that helper peptides might interact with the same critical residues on MHC class II that is targeted by DM.
Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85715, USA.
Chih-Ling
CL
Chou
Saied
S
Mirshahidi
Katherine Wailen
KW
Su
AeRyon
A
Kim
Kedar
K
Narayan
Stanislav
S
Khoruzhenko
Minzhen
M
Xu
Scheherazade
S
Sadegh-Nasseri
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D049109:Cell Proliferation; D006681:HLA-D Antigens / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000276:immunology; D006801:Humans; D007114:Immunization; D007313:Insecta; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D050505:Mutant Proteins; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013816:Thermodynamics
D006681:HLA-D Antigens; C084245:HLA-DM antigens; D015798:HLA-DR1 Antigen; D050505:Mutant Proteins; D010455:Peptides