title: Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity.
abstract: Immunoglobulins (Igs) are a crown jewel of jawed vertebrate evolution. Through recombination and mutation of small numbers of genes, Igs can specifically recognize a vast variety of natural and man-made organic molecules. Jawless vertebrates evolved a parallel system of humoral immunity, which recognizes antigens not with Ig, but with a structurally unrelated receptor called the variable lymphocyte receptor B (VLRB). We exploited the convergent evolution of Ig and VLRB antibodies (Abs) to investigate if intrinsic chemical features of foreign proteins determine their antigenicity and immunogenicity. Surprisingly, we find lamprey VLRB and mouse Ig responses to influenza A virus are extremely similar. Each focuses ~80% of the response on hemagglutinin (HA), mainly through recognition of the major antigenic sites in the HA globular head domain. Our findings predict basic conservation of Ab responses to protein antigens, strongly supporting the use of animal models for understanding human Ab responses to viruses and protein immunogens.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: Meghan O
authors.initials: MO
authors.lastname: Altman
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Bennink
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, United States.
authors.forename: Brantley R
authors.initials: BR
authors.lastname: Herrin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D005393:Fish Diseases / Q000276:immunology*; D029941:Fish Proteins / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007798:Lampreys / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000662:veterinary*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D029941:Fish Proteins; D011971:Receptors, Immunologic
keywords: antibodies; antigenicity; hemagglutinin; immunodominance; immunology; infectious disease; influenza; lamprey; microbiology; mouse