Mutations in or near the fusion peptide of the influenza virus hemagglutinin affect an antigenic site in the globular region

Yewdell, Jonathan W.; Taylor, Alexander H.; Yellen, Amy; Caton, Andrew J.; Gerhard, Walter; Bächi, Thomas

doi:10.1128/jvi.67.2.933-942.1993

Cited by 58 publications

(27 citation statements)

References 33 publications

(30 reference statements)

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“…W/cm 2 of UV light for 15 min on ice. DTBP, purchased from Pierce, was used to cross-link UV-inactivated virus as described [19]. Briefly, UVinactivated influenza particles were incubated for 3 h at room temperature with 1 mg/ml DTBP dissolved in 0.2 M triethanolamine-HCl (pH 8.5).…”

Section: Cells and Antigensmentioning

confidence: 99%

Peptide loading onto recycling HLA-DR molecules occurs in early endosomes

Pinet

Long

1998

Eur. J. Immunol.

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Presentation of exogenous antigens to MHC class II-restricted T cells can follow two different processing pathways. The classical pathway requires newly synthesized MHC class II molecules, invariant chain and HLA-DM expression, whereas the alternative pathway is independent of protein synthesis, invariant chain and HLA-DM. In both cases, MHC class II molecules associate with peptides derived from exogenous antigens that have been processed in endocytic compartments. Different endosomal/prelysosomal compartments where peptide/MHC class II complexes and HLA-DM molecules accumulate have been described. We show here that the alternative pathway uses an earlier compartment than the classical pathway. Experiments with chemically cross-linked antigen suggest that recycling MHC class II molecules present rapidly degraded antigens, leading to a rapid immune response to exogenously added influenza virus proteins.

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Section: Cells and Antigensmentioning

confidence: 99%

Peptide loading onto recycling HLA-DR molecules occurs in early endosomes

Pinet

Long

1998

Eur. J. Immunol.

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“…There is mounting evidence that the entire hemagglutinin molecule may be necessary to stabilize the membrane fusion site (White, 1992). In addition, there is evidence that the fusion peptide also serves to stabilize the structure of the hemagglutinin protein at neutral pH (Carr and Kim, 1993;Yewdell et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Micropipette manipulation technique for the monitoring of pH-dependent membrane lysis as induced by the fusion peptide of influenza virus

Soltesz

Hammer

1995

Biophysical Journal

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We have assembled a micropipette aspiration assay to measure membrane destabilization events in which large (20-30 microns diameter) unilamellar vesicles are manipulated and exposed to membrane destabilizing agents. Single events can be seen with a light microscope and are recorded using both a video camera and a photomultiplier tube. We have performed experiments with a wild-type fusion peptide from influenza virus (X31) and found that it induces pH-dependent, stochastic lysis of large unilamellar vesicles. The rate and extent of lysis are both maximum at pH 5; the maximum rate of lysis is 0.018 s-1 at pH 5. An analysis of our data indicates that the lysis is not correlated either to the size of the vesicles or to the tension created in the vesicle membranes by aspiration.

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“…Direct Ab binding studies are much to be preferred in dissecting OAS mechanistically because they provide the most direct and comprehensive measure of anti-HA B cell responses. Further, it is becoming clear that Abs with weak or nondetectable HI or VN activities in vitro, including Abs specific for the stem or cryptic epitopes exposed by HA breathing (Yewdell et al 1993;Watanabe et al 2019), can exert antiviral activity in vivo via Fcreceptor (FcR)-based innate cellular immunity (DiLillo et al 2016;He et al 2016).…”

Section: Misconception: Oas Is a Constant Feature Of Iav Immunitymentioning

confidence: 99%

Original Antigenic Sin: How Original? How Sinful?

Yewdell

Santos

2020

Cold Spring Harb Perspect Med

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We review the phenomenon of "original antigenic sin" (OAS) in antibody responses to influenza A virus (IAV) infection or vaccination. OAS refers to the preferential induction of antibodies with higher affinity to priming versus boosting immunogens. We emphasize its mechanistic basis and origins in the basic immunobiology of B-cell responses to myriad immunogens. We tabulate 23 studies in animals and humans to show that the magnitude of OAS depends on many variables. We discuss a number of misconceptions about OAS, examine the extent to which OAS is sinful, and argue that OAS is evolutionary selected and not a deleterious by-product of selection for other features of the immune response. We end by raising questions regarding the mechanistic basis of OAS whose answers could contribute to improving influenza virus vaccines on the road to the holy grail of a "universal" influenza vaccine.

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Mutations in or near the fusion peptide of the influenza virus hemagglutinin affect an antigenic site in the globular region

Cited by 58 publications

References 33 publications

Peptide loading onto recycling HLA-DR molecules occurs in early endosomes

Peptide loading onto recycling HLA-DR molecules occurs in early endosomes

Micropipette manipulation technique for the monitoring of pH-dependent membrane lysis as induced by the fusion peptide of influenza virus

Original Antigenic Sin: How Original? How Sinful?

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