Molecular analysis of original antigenic sin. I. Clonal selection, somatic mutation, and isotype switching during a memory B cell response.

Fish, S; Zenowich, Elizabeth; Fleming, Mark D.; Manser, Tim

doi:10.1084/jem.170.4.1191

Cited by 62 publications

(51 citation statements)

References 48 publications

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“…Exposure to a second heterologous flu virus boosted Ab responses against the priming strain of the virus, with only modest responses directed against the heterologous virus (24,33,34). It has been shown that in the presence of anti-hapten Ab, memory B cells are preferentially activated in vivo by a structurally related haptenic analog for the priming hapten (35,36). Memory B cell responses to a given Ag are dominant over naive B cell responses (37).…”

Section: Discussionmentioning

confidence: 99%

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Liu

Hardy

et al. 2003

The Journal of Immunology

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Priming to Ag can inhibit subsequent induction of an immune response to a new epitope incorporated into that Ag, a phenomenon referred to as original antigenic sin. In this study, we show that prior immunity to a virus capsid can inhibit subsequent induction of the IFN-γ effector T cell response to a novel CD8-restricted antigenic epitope associated with the virus capsid. Inhibition does not involve Ab to the virus capsid, as it is observed in animals lacking B cells. CD8-restricted virus-specific T cell responses are not required, as priming to virus without CTL induction is associated with inhibition. However, IL-10−/− mice, in contrast to IL-10+/+ mice, generate CD8 T cell and Ab responses to novel epitopes incorporated into a virus capsid, even when priming to the capsid has resulted in high titer Ab to the capsid. Furthermore, capsid-primed mice, unable to mount a response to a novel epitope in the capsid protein, are nevertheless able to respond to the same novel epitope delivered independently of the capsid. Thus, inhibition of responsiveness to a novel epitope in a virus-primed animal is a consequence of secretion of IL-10 in response to presented Ag, which inhibits local generation of new CD8 IFN-γ-secreting effector T cells. Induction of virus- or tumor Ag-specific CD8 effector T cells in the partially Ag-primed host may thus be facilitated by local neutralization of IL-10.

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Section: Discussionmentioning

confidence: 99%

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Liu

Hardy

et al. 2003

The Journal of Immunology

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“…Serum samples were obtained when the first biopsy was taken (untreated coeliac disease), in remission on a gluten-free diet (treated), and/or at relapse after reintroduction of gluten (challenged). Anti-blactoglobulin antibody levels and avidities were analysed in sera from 16 children with untreated disease (median age 12 months, range [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and nine with treated disease (median age 35 months, range . Antigliadin antibody levels and avidities were measured in 16 untreated coeliac children (median age 15 months, range 10-24), 11 treated cases (median age 32 months, range 17-57) and in eight coeliac children at relapse on gluten challenge (median age 45 months, range 32-53).…”

Section: Patientsmentioning

confidence: 99%

Avidity progression of dietary antibodies in healthy and coeliac children

Saalman

Dahlgren

Fällström

et al. 2003

Clinical and Experimental Immunology

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SUMMARYIn most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. b -lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against b -lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against b -lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-b -lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.

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“…41 The sin response is derived from a small but stable memory B cell clone with somatically mutated V regions induced by the primary infection. 42 This phenomenon should be considered in serum diagnostics of these and other closely related bunyaviruses such as among the members of the California serogroup.…”

Section: Serosurveymentioning

confidence: 99%

Cache Valley and Potosi viruses (Bunyaviridae) in white-tailed deer (Odocoileus virginianus): experimental infections and antibody prevalence in natural populations.

Blackmore

Grimstad²

1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Cache Valley virus (CVV) and Potosi virus (POTV) are two closely related mosquito-borne viruses (Bunyaviridae: Bunyamwera group) that appear to circulate in several regions of the United States, especially the Midwest. We determined the prevalence of specific neutralizing antibodies to both viruses in Indiana white-tailed deer and conducted infection experiments to assess whether deer could serve as an vertebrate-amplifying host. Crossinfection experiments also were carried out to investigate the level of antibody cross-reactivity and cross-protection between the two viruses. The seroprevalence rate was high for both CVV (Ͼ 66%) and POTV (Ͼ 43%) in adult deer statewide. Antibodies neutralizing CVV were more common among deer harvested in the northern part of Indiana whereas the prevalence of POTV antibodies suggested a more southern distribution for this virus. Experimental infections of captive deer showed that they may serve as amplifying hosts for either virus. Deer infected with CVV or POTV developed a 1-3-day viremia with 3.0 and 4.1 log 10 plaque-forming units/ml mean peak titers, respectively. However, significant levels of antibody cross-reactivity between the two viruses were observed. Viremia was lower and shorter when animals immune to either CVV or POTV were cross-infected with the alternate virus and antibody responses following cross-infections resembled original antigenic sin with higher titers of antibodies against the primary agent.

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Molecular analysis of original antigenic sin. I. Clonal selection, somatic mutation, and isotype switching during a memory B cell response.

Cited by 62 publications

References 48 publications

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Avidity progression of dietary antibodies in healthy and coeliac children

Cache Valley and Potosi viruses (Bunyaviridae) in white-tailed deer (Odocoileus virginianus): experimental infections and antibody prevalence in natural populations.

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