Heterodimer HLA-DM Fused with Constant Fragment of the Heavy Chain of the Human Immunoglobulin Accelerates Influenza Hemagglutinin HA306-318 Loading to HLA-DR1.
Major histocompatibility complex class II (MHC II) plays an important role not only in the adaptive immune responses to foreign pathogens, but also in the development of some autoimmune diseases. Non-classical MHC, HLA-DM is directly involved in MHC II loading with the peptide. To study this process, we synthesized recombinant proteins HLA-DR1 and HLA-DM. α/β-Chains of DR1 heterodimer contained C-terminal leucine domains of the fos and jun factors, respectively. Each DM chain contained constant fragment of human antibody heavy chain fused via a long linker domain. In addition, DM α-chain carried N165D substitution suppressing potential glycosylation at this site. We observed significant acceleration of DR1 peptide loading with influenza HA306-318 hemagglutinin in the presence of DM, which indicates functionality of recombinant DR1-DM protein couple. Our results can be used to study the presentation of other viral and self-antigens and can become the basis for the development of new drug modeling.
M. V. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
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Mamedov
M. V. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
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Ponomarenko
M. V. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia. alexey.belogurov.jr@gmail.ru.
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Belogurov
M. V. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
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Gabibov
D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D004331:Drosophila melanogaster; D057809:HEK293 Cells; D006681:HLA-D Antigens / Q000494:pharmacology*; D015798:HLA-DR1 Antigen / Q000502:physiology*; D006367:HeLa Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000494:pharmacology*; D007143:Immunoglobulin Heavy Chains / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
D006681:HLA-D Antigens; C084245:HLA-DM antigens; D015798:HLA-DR1 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C086595:influenza hemagglutinin (306-318)
HLA-DM; HLA-DR1; hemagglutinin peptide HA; major histocompatibility complex class II