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Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity.

Altman MO, Bennink JR, Yewdell JW, Herrin BR - Elife (2015)

Bottom Line: 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.Each focuses ~80% of the response on hemagglutinin (HA), mainly through recognition of the major antigenic sites in the HA globular head domain.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States.

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.

No MeSH data available.


Related in: MedlinePlus

Lamprey VLRBs bind to hemagglutinin and neutralize infection.(A) Plasma from PR8-immunized lamprey inhibits PR8 hemagglutination at a 1:30 plasma dilution, but did not inhibit hemagglutination by either HK or B/Lee at any dilution. Data are representative of two experiments. (B) MDCK cells were infected with an MOI 0.07 of PR8 in the presence of titrated mAb supernatants (H17L2 against PR8 or control 1.2F4 against influenza B/Lee) or lamprey plasma (L9 vs Naïve). After 8 hr cells were fixed, double-stained with anti-HA and anti-NP Igs. Cells positive for either HA or NP by flow cytometry were considered infected. Data from four independent experiments were normalized to control for different percentages of infection between experiments and fit to a variable dose–response curve. The best-fit, calculated infectious dose 50 (ID50) was significantly lower for both the immunized plasma and PR8 specific Ig (***p < 0.001).DOI:http://dx.doi.org/10.7554/eLife.07467.009
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fig4: Lamprey VLRBs bind to hemagglutinin and neutralize infection.(A) Plasma from PR8-immunized lamprey inhibits PR8 hemagglutination at a 1:30 plasma dilution, but did not inhibit hemagglutination by either HK or B/Lee at any dilution. Data are representative of two experiments. (B) MDCK cells were infected with an MOI 0.07 of PR8 in the presence of titrated mAb supernatants (H17L2 against PR8 or control 1.2F4 against influenza B/Lee) or lamprey plasma (L9 vs Naïve). After 8 hr cells were fixed, double-stained with anti-HA and anti-NP Igs. Cells positive for either HA or NP by flow cytometry were considered infected. Data from four independent experiments were normalized to control for different percentages of infection between experiments and fit to a variable dose–response curve. The best-fit, calculated infectious dose 50 (ID50) was significantly lower for both the immunized plasma and PR8 specific Ig (***p < 0.001).DOI:http://dx.doi.org/10.7554/eLife.07467.009

Mentions: Next we examined the functionality of the lamprey anti-HA response as revealed by hemagglutination inhibition (HI) or infectivity neutralization assays. HI measures the ability of Abs to block HA-mediated IAV attachment to erythrocyte surface terminal sialic acids. PR8-immunized lamprey plasma gave HI titers of 1:30 against PR8, but <1:5 against an H3N2 IAV and B/Lee, an influenza B virus, which is serologically totally distinct from IAV (Figure 4A). Immune lamprey plasma also significantly inhibited PR8 infectivity in MDCK cells relative to naïve plasma (Figure 4B).10.7554/eLife.07467.009Figure 4.Lamprey VLRBs bind to hemagglutinin and neutralize infection.


Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity.

Altman MO, Bennink JR, Yewdell JW, Herrin BR - Elife (2015)

Lamprey VLRBs bind to hemagglutinin and neutralize infection.(A) Plasma from PR8-immunized lamprey inhibits PR8 hemagglutination at a 1:30 plasma dilution, but did not inhibit hemagglutination by either HK or B/Lee at any dilution. Data are representative of two experiments. (B) MDCK cells were infected with an MOI 0.07 of PR8 in the presence of titrated mAb supernatants (H17L2 against PR8 or control 1.2F4 against influenza B/Lee) or lamprey plasma (L9 vs Naïve). After 8 hr cells were fixed, double-stained with anti-HA and anti-NP Igs. Cells positive for either HA or NP by flow cytometry were considered infected. Data from four independent experiments were normalized to control for different percentages of infection between experiments and fit to a variable dose–response curve. The best-fit, calculated infectious dose 50 (ID50) was significantly lower for both the immunized plasma and PR8 specific Ig (***p < 0.001).DOI:http://dx.doi.org/10.7554/eLife.07467.009
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4552221&req=5

fig4: Lamprey VLRBs bind to hemagglutinin and neutralize infection.(A) Plasma from PR8-immunized lamprey inhibits PR8 hemagglutination at a 1:30 plasma dilution, but did not inhibit hemagglutination by either HK or B/Lee at any dilution. Data are representative of two experiments. (B) MDCK cells were infected with an MOI 0.07 of PR8 in the presence of titrated mAb supernatants (H17L2 against PR8 or control 1.2F4 against influenza B/Lee) or lamprey plasma (L9 vs Naïve). After 8 hr cells were fixed, double-stained with anti-HA and anti-NP Igs. Cells positive for either HA or NP by flow cytometry were considered infected. Data from four independent experiments were normalized to control for different percentages of infection between experiments and fit to a variable dose–response curve. The best-fit, calculated infectious dose 50 (ID50) was significantly lower for both the immunized plasma and PR8 specific Ig (***p < 0.001).DOI:http://dx.doi.org/10.7554/eLife.07467.009
Mentions: Next we examined the functionality of the lamprey anti-HA response as revealed by hemagglutination inhibition (HI) or infectivity neutralization assays. HI measures the ability of Abs to block HA-mediated IAV attachment to erythrocyte surface terminal sialic acids. PR8-immunized lamprey plasma gave HI titers of 1:30 against PR8, but <1:5 against an H3N2 IAV and B/Lee, an influenza B virus, which is serologically totally distinct from IAV (Figure 4A). Immune lamprey plasma also significantly inhibited PR8 infectivity in MDCK cells relative to naïve plasma (Figure 4B).10.7554/eLife.07467.009Figure 4.Lamprey VLRBs bind to hemagglutinin and neutralize infection.

Bottom Line: 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.Each focuses ~80% of the response on hemagglutinin (HA), mainly through recognition of the major antigenic sites in the HA globular head domain.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States.

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.

No MeSH data available.


Related in: MedlinePlus