Heterodimer HLA-DM Fused with Constant Fragment of the Heavy Chain of the Human Immunoglobulin Accelerates Influenza Hemagglutinin HA306–318 Loading to HLA-DR1

• Published in: Bulletin of experimental biology and medicine Vol. 161; no. 1; pp. 92 - 95
• Main Authors: Mamedov, A. E., Ponomarenko, N. A., Belogurov, A. A., Gabibov, A. G.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2016
• Subjects: Adaptive Immunity; Animals; Antigen Presentation - drug effects; Autoimmune Diseases - immunology; Autoimmunity; Biomedical and Life Sciences; Biomedicine; Cell Biology; Drosophila melanogaster; HEK293 Cells; HeLa Cells; Hemagglutinin Glycoproteins, Influenza Virus - immunology; HLA-D Antigens - pharmacology; HLA-DR1 Antigen - physiology; Humans; Immunoglobulin Constant Regions - pharmacology; Immunoglobulin Heavy Chains - pharmacology; Internal Medicine; Laboratory Medicine; Pathology; Peptide Fragments - immunology; Protein Binding; Recombinant Fusion Proteins - pharmacology; HLA-DR1; HLA-DM; major histocompatibility complex class II; hemagglutinin peptide HA
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-016-3353-y

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 HA 306–318 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.