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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

PR8 immunized lamprey plasma binds purified NP protein, but not purified M1 by ELISA.Purified NP or M1 protein were adsorbed to ELISA plates and probed with mouse sera (n = 2) or lamprey plasma from either immunized (n = 4) or naïve (n = 2) animals. Data were analyzed by two-way ANOVA followed by Bonferroni multiple comparison using PRISM software (*p < 0.0001). Both PR8-immune mouse sera and lamprey plasma bound NP better than unimmunized control. Neither bound M1 protein. mAbs M2-1C6 for M1 and HB65 for NP are shown to confirm proper folding of purified protein on plate.DOI:http://dx.doi.org/10.7554/eLife.07467.008
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fig3s3: PR8 immunized lamprey plasma binds purified NP protein, but not purified M1 by ELISA.Purified NP or M1 protein were adsorbed to ELISA plates and probed with mouse sera (n = 2) or lamprey plasma from either immunized (n = 4) or naïve (n = 2) animals. Data were analyzed by two-way ANOVA followed by Bonferroni multiple comparison using PRISM software (*p < 0.0001). Both PR8-immune mouse sera and lamprey plasma bound NP better than unimmunized control. Neither bound M1 protein. mAbs M2-1C6 for M1 and HB65 for NP are shown to confirm proper folding of purified protein on plate.DOI:http://dx.doi.org/10.7554/eLife.07467.008

Mentions: Reciprocal immunization of lampreys with HK virus (Figure 3C) confirmed the dominance of HA. This experiment also provides a direct control for the specificity of lamprey VLRB for H1N1 vs H3N2 glycoproteins. Flow cytometry of cells expressing either HA, NA, NP, M1/M2 or NS1 (which is present in virions [Hutchinson et al., 2014]) from transfected cDNAs stained with lamprey plasma showed that PR8 induced detectable VLRB responses to HA and NA but not NP, M1, M2, or NS1 (Figure 3—figure supplement 2). Similarly, mouse serum Ig was positive against HA and NA and negative for M1 + M2, although there was a response to NP. While lamprey plasma did not bind plasmid expressed NP by flow, in ELISA, both immune lamprey plasma and mouse sera bound plated NP, but neither bound M1 (Figure 3—figure supplement 3). The lack of NP binding in the flow assay is most likely spurious; due to limited VLRB access to NP within permeabilized cells, or low signal.


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

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

PR8 immunized lamprey plasma binds purified NP protein, but not purified M1 by ELISA.Purified NP or M1 protein were adsorbed to ELISA plates and probed with mouse sera (n = 2) or lamprey plasma from either immunized (n = 4) or naïve (n = 2) animals. Data were analyzed by two-way ANOVA followed by Bonferroni multiple comparison using PRISM software (*p < 0.0001). Both PR8-immune mouse sera and lamprey plasma bound NP better than unimmunized control. Neither bound M1 protein. mAbs M2-1C6 for M1 and HB65 for NP are shown to confirm proper folding of purified protein on plate.DOI:http://dx.doi.org/10.7554/eLife.07467.008
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552221&req=5

fig3s3: PR8 immunized lamprey plasma binds purified NP protein, but not purified M1 by ELISA.Purified NP or M1 protein were adsorbed to ELISA plates and probed with mouse sera (n = 2) or lamprey plasma from either immunized (n = 4) or naïve (n = 2) animals. Data were analyzed by two-way ANOVA followed by Bonferroni multiple comparison using PRISM software (*p < 0.0001). Both PR8-immune mouse sera and lamprey plasma bound NP better than unimmunized control. Neither bound M1 protein. mAbs M2-1C6 for M1 and HB65 for NP are shown to confirm proper folding of purified protein on plate.DOI:http://dx.doi.org/10.7554/eLife.07467.008
Mentions: Reciprocal immunization of lampreys with HK virus (Figure 3C) confirmed the dominance of HA. This experiment also provides a direct control for the specificity of lamprey VLRB for H1N1 vs H3N2 glycoproteins. Flow cytometry of cells expressing either HA, NA, NP, M1/M2 or NS1 (which is present in virions [Hutchinson et al., 2014]) from transfected cDNAs stained with lamprey plasma showed that PR8 induced detectable VLRB responses to HA and NA but not NP, M1, M2, or NS1 (Figure 3—figure supplement 2). Similarly, mouse serum Ig was positive against HA and NA and negative for M1 + M2, although there was a response to NP. While lamprey plasma did not bind plasmid expressed NP by flow, in ELISA, both immune lamprey plasma and mouse sera bound plated NP, but neither bound M1 (Figure 3—figure supplement 3). The lack of NP binding in the flow assay is most likely spurious; due to limited VLRB access to NP within permeabilized cells, or low signal.

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