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Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

French MA, Abudulai LN, Fernandez S - Vaccines (Basel) (2013)

Bottom Line: The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV.These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses.Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs.

View Article: PubMed Central - PubMed

Affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, Australia. martyn.french@uwa.edu.au.

ABSTRACT
The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

No MeSH data available.


Related in: MedlinePlus

Isotype diversification of an IgG antibody response. IgG antibody isotype switching during B-cell differentiation in germinal centres results from class switch recombination of immunoglobulin heavy chain genes from “downstream” (IgG3 and IgG1) to “upstream” (IgG2 and IgG4) isotypes regulated by co-stimulatory molecules (CD40L and inducible co-stimulator (ICOS)) and cytokines (IL-4, IL-10 and IL-21). Pro-inflammatory cytokines (IL-2, IL-6 and IFN-γ) enhance immunoglobulin production with IFN-γ particularly increasing IgG2 production. CD4+ T-cell production of both IL-21 and IFN-γ is impaired by HIV infection.
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vaccines-01-00328-f001: Isotype diversification of an IgG antibody response. IgG antibody isotype switching during B-cell differentiation in germinal centres results from class switch recombination of immunoglobulin heavy chain genes from “downstream” (IgG3 and IgG1) to “upstream” (IgG2 and IgG4) isotypes regulated by co-stimulatory molecules (CD40L and inducible co-stimulator (ICOS)) and cytokines (IL-4, IL-10 and IL-21). Pro-inflammatory cytokines (IL-2, IL-6 and IFN-γ) enhance immunoglobulin production with IFN-γ particularly increasing IgG2 production. CD4+ T-cell production of both IL-21 and IFN-γ is impaired by HIV infection.

Mentions: Regulation of immunoglobulin isotype switching is mediated primarily by molecules expressed on, or produced by, TFH-cells [76]. The most important are the co-stimulatory molecules, CD40 ligand and inducible co-stimulator (ICOS), as exemplified by the association of immunoglobulin deficiency with deficiency of these molecules [79,80], and the cytokines, IL-4, IL-10 and IL-21, as exemplified by the restoration of immunoglobulin production by B-cells from patients with IgA deficiency or common variable immunodeficiency disorder when cultured with these cytokines [81,82,83]. The co-inhibitory molecule programmed death (PD)-1 is also highly expressed by TFH-cells, and ligation by the ligand PD-L1 has been shown to down-regulate ICOS expression and IL-21 production and possibly contribute to TFH-cell dysfunction caused by HIV infection [84]. Pro-inflammatory cytokines, such IL-2, IL-6 and IFN-γ, also contribute to isotype diversification of IgG antibodies, but primarily by enhancing production of IgG subclasses rather than initiating isotype switching [85,86,87,88,89] (Figure 1).


Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

French MA, Abudulai LN, Fernandez S - Vaccines (Basel) (2013)

Isotype diversification of an IgG antibody response. IgG antibody isotype switching during B-cell differentiation in germinal centres results from class switch recombination of immunoglobulin heavy chain genes from “downstream” (IgG3 and IgG1) to “upstream” (IgG2 and IgG4) isotypes regulated by co-stimulatory molecules (CD40L and inducible co-stimulator (ICOS)) and cytokines (IL-4, IL-10 and IL-21). Pro-inflammatory cytokines (IL-2, IL-6 and IFN-γ) enhance immunoglobulin production with IFN-γ particularly increasing IgG2 production. CD4+ T-cell production of both IL-21 and IFN-γ is impaired by HIV infection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494226&req=5

vaccines-01-00328-f001: Isotype diversification of an IgG antibody response. IgG antibody isotype switching during B-cell differentiation in germinal centres results from class switch recombination of immunoglobulin heavy chain genes from “downstream” (IgG3 and IgG1) to “upstream” (IgG2 and IgG4) isotypes regulated by co-stimulatory molecules (CD40L and inducible co-stimulator (ICOS)) and cytokines (IL-4, IL-10 and IL-21). Pro-inflammatory cytokines (IL-2, IL-6 and IFN-γ) enhance immunoglobulin production with IFN-γ particularly increasing IgG2 production. CD4+ T-cell production of both IL-21 and IFN-γ is impaired by HIV infection.
Mentions: Regulation of immunoglobulin isotype switching is mediated primarily by molecules expressed on, or produced by, TFH-cells [76]. The most important are the co-stimulatory molecules, CD40 ligand and inducible co-stimulator (ICOS), as exemplified by the association of immunoglobulin deficiency with deficiency of these molecules [79,80], and the cytokines, IL-4, IL-10 and IL-21, as exemplified by the restoration of immunoglobulin production by B-cells from patients with IgA deficiency or common variable immunodeficiency disorder when cultured with these cytokines [81,82,83]. The co-inhibitory molecule programmed death (PD)-1 is also highly expressed by TFH-cells, and ligation by the ligand PD-L1 has been shown to down-regulate ICOS expression and IL-21 production and possibly contribute to TFH-cell dysfunction caused by HIV infection [84]. Pro-inflammatory cytokines, such IL-2, IL-6 and IFN-γ, also contribute to isotype diversification of IgG antibodies, but primarily by enhancing production of IgG subclasses rather than initiating isotype switching [85,86,87,88,89] (Figure 1).

Bottom Line: The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV.These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses.Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs.

View Article: PubMed Central - PubMed

Affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, Australia. martyn.french@uwa.edu.au.

ABSTRACT
The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

No MeSH data available.


Related in: MedlinePlus