“…Effective help for B-cell responses to virus surface antigens by TH clones specific for internal proteins has been reported by several other groups investigating the antibody response to influenza (40,41), hepatitis B (42), and rabies (43) viruses. Further, a type of intrastructural/intermolecular inhibition has been shown to occur in the antibody response to influenza virus NA (44)(45)(46).…”
When a helper T-cell (TH) clone specific for the hemagglutinin, neuraminidase, matrix protein, or nucleoprotein of influenza strain A/PR/8/34 is adoptively transferred to athymic mice 1 day after virus infection the anti-viral antibody response of the mouse is enhanced. This response is directed predominantly to the hemagglutinin and requires associative T-cell-B-cell interactions. Delaying For a resting B cell to become activated and produce antibodies, a second signal, beyond the occupancy of its surface immunoglobulin receptor by antigen, is required (1, 2). This signal is in most cases provided by helper T cells (TH). Two types of T-cell help have been described (3, 4).Cognate help is major histocompatibility complex-restricted and requires that the antigenic determinants recognized by the B cell and by the T cell be covalently linked (5)(6)(7)(8). This type of help is thought to occur through a direct interaction between the TH and B cells and to result in the transduction of a signal to the B cell in the form of locally released factors and/or crosslinking of surface molecules. This signal enables the B cell to go on to proliferate and differentiate into an antibody-secreting B-cell clone (9-13). Bystander help, in contrast to cognate help, is thought to occur through the release of T-cell-derived factors that act nonspecifically on activated B cells (14)(15)(16)(17). No direct link between the antigenic determinants recognized by the T cell and the B cell is, therefore, required.
4446The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
“…Effective help for B-cell responses to virus surface antigens by TH clones specific for internal proteins has been reported by several other groups investigating the antibody response to influenza (40,41), hepatitis B (42), and rabies (43) viruses. Further, a type of intrastructural/intermolecular inhibition has been shown to occur in the antibody response to influenza virus NA (44)(45)(46).…”
When a helper T-cell (TH) clone specific for the hemagglutinin, neuraminidase, matrix protein, or nucleoprotein of influenza strain A/PR/8/34 is adoptively transferred to athymic mice 1 day after virus infection the anti-viral antibody response of the mouse is enhanced. This response is directed predominantly to the hemagglutinin and requires associative T-cell-B-cell interactions. Delaying For a resting B cell to become activated and produce antibodies, a second signal, beyond the occupancy of its surface immunoglobulin receptor by antigen, is required (1, 2). This signal is in most cases provided by helper T cells (TH). Two types of T-cell help have been described (3, 4).Cognate help is major histocompatibility complex-restricted and requires that the antigenic determinants recognized by the B cell and by the T cell be covalently linked (5)(6)(7)(8). This type of help is thought to occur through a direct interaction between the TH and B cells and to result in the transduction of a signal to the B cell in the form of locally released factors and/or crosslinking of surface molecules. This signal enables the B cell to go on to proliferate and differentiate into an antibody-secreting B-cell clone (9-13). Bystander help, in contrast to cognate help, is thought to occur through the release of T-cell-derived factors that act nonspecifically on activated B cells (14)(15)(16)(17). No direct link between the antigenic determinants recognized by the T cell and the B cell is, therefore, required.
4446The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
“…Correspondingly, coapplication of an IL-12-encoding plasmid as a genetic adjuvant also failed in this regard. Therefore, we tried to modulate the Ab subclass distribution by employing ISH, which is known to increase humoral immune responses against viral surface proteins (21)(22)(23)25). The exchange of Env-specific CD4 + T cells with GagPol-specific cells, which secreted little to no Th2-associated cytokines, imprinted the IgG2a-dominated phenotype of the Gag-specific humoral immune FIGURE 7.…”
Section: Discussionmentioning
confidence: 99%
“…It has been reported that Th cells specific for *Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum 44801, Germany; internal proteins of influenza or hepatitis B virus can support the development of Ab responses to their respective surface proteins after virus infection or upon immunization with viral particles (21)(22)(23). The molecular mechanism explaining these observations is based on BCR-dependent uptake of entire virus particles by B cells specific for the surface protein of the virion and subsequent presentation of Th cell epitopes from the surface protein and internal viral proteins on MHC-II molecules of these B cells.…”
The importance of Fc-dependent effector functions of Abs induced by vaccination is increasingly recognized. However, vaccination of mice against HIV envelope (Env) induced a skewed Th cell response leading to Env-specific Abs with reduced effector function. To overcome this bias, GagPol-specific Th cells were harnessed to provide intrastructural help for Env-specific B cells after immunization with virus-like particles containing GagPol and Env. This led to a balanced Env-specific humoral immune response with a more inflammatory Fc glycan profile. The increased quality in the Ab response against Env was confirmed by FcγR activation assays. Because the Env-specific Th cell response was also biased in human vaccinees, intrastructural help is an attractive novel approach to increase the efficacy of prophylactic HIV Env-based vaccines and may also be applicable to other particulate vaccines.
“…This model, based directly on the original demonstration by Lake and Mitchison, finds support in analyses of immune response to viral particles: T cell responses directed against internal viral proteins, exposed after antigen processing of intact virus, may provide help to B cells that initially bind exposed surface components via surface Ig (51,52). As one example, T cells from mice primed by the nucleocapsid (core) protein of hepatitis B virus (HBcAg), or by one of its immunodominant peptides, could drive antibody production against hepatitis B surface antigen (HBsAg), provided the primed mice were boosted with intact virus; doses of the latter were adjusted to avoid antibody responses to HBsAg in the absence of the initial immunization with HBcAg ( Figure 1) (53).…”
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