Generation of CD4+ and CD8+ T Lymphocyte Responses by Dendritic Cells Armed with PSA/Anti-PSA (Antigen/Antibody) Complexes

Berlyn, Kathleen A.; Schultes, Birgit C.; Leveugle, Béatrice; Noujaim, A.A.; Alexander, Richard B.; Mann, Dean L.

doi:10.1006/clim.2001.5115

Cited by 61 publications

(33 citation statements)

References 25 publications

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“…Immature DCs were cultured in the presence of recombinant human interleukin-4 and recombinant human granulocyte macrophage colony -stimulating factor (PeproTech) at 100 ng/mL each for 7 days; half of the media with fresh cytokines was replaced on day 4. To ensure optimal antigen uptake and processing, PSA or cell lysates were added at different concentrations to immature DCs on day 4 after initiation of DC culture for 6 to 8 hours followed by incubation with recombinant human tumor necrosis factor a (30 ng/mL) and recombinant human IFNa (50 units/mL; R&D Systems, Inc., Minneapolis, MN) for the remaining 3 days (15). The phenotype of mature DCs was assessed by staining with anti-CD14-FITC (<1%), anti-CD83-PE (18-22%), anti-CD80-PE (13-25%), anti-HLA-DR-PE (70-80%), and anti-CD86-FITC (98%; all mAbs from Pharmingen).…”

Section: Methodsmentioning

confidence: 99%

Identification of HLA-DRB1*1501–Restricted T-cell Epitopes from Prostate-Specific Antigen

Klyushnenkova

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Oberle

et al. 2005

Clinical Cancer Research

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The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 Tcells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II^restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)^derived MHC class II^restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA [171][172][173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190] and PSA 221-240 , which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.

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Section: Methodsmentioning

confidence: 99%

Identification of HLA-DRB1*1501–Restricted T-cell Epitopes from Prostate-Specific Antigen

Klyushnenkova

Link

Oberle

et al. 2005

Clinical Cancer Research

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“…This represents another example whereby the immunogenicity of epitopes other than those recognized by the modulatory antibody was affected. To test whether exposure of antigen presenting cells to IC compared to antigen alone would influence the resultant T-cell response, a study was undertaken in which DC were exposed to prostatespecific antigen (PSA) or PSA combined with an anti-PSA MAb (13). Both CD4-and CD8-T-cell responses were detected following DC stimulation with the IC, whereas a CD4 response predominated when DC were stimulated with PSA alone.…”

Section: Immunization With Immune Complexesmentioning

confidence: 99%

Antibody-Mediated Immunomodulation: a Strategy To Improve Host Responses against Microbial Antigens

Brady

2005

Infect Immun

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“…Immune complexes have, however, been successfully utilized for vaccines against a number of antigens such as hepatitis (37,70), Newcastle disease virus (47), prostate-specific antigens (13), etc., and their role in antigen uptake by dendritic cells have been studied (60). Thus, in the normal physiological in vivo conditions, virus and viral antigens are present not only in soluble forms but to a large extent as viral antigen-antibody complexes and, as such, these must be internalized for eventual elimination.…”

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confidence: 99%

Evidence for Antibody-Mediated Enhancement of Simian Immunodeficiency Virus (SIV) Gag Antigen Processing and Cross Presentation in SIV-Infected Rhesus Macaques

Villinger¹,

Mayne²,

Boštík³

et al. 2003

J Virol

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By using the dominant simian immunodeficiency virus (SIV) Gag Mamu-A01 restricted major histocompatibility complex (MHC) class I epitope p11CM, we demonstrate antibody-mediated enhanced MHC class I cross presentation of SIV Gag. In vitro restimulation of peripheral blood mononuclear cells from SIV-infected rhesus macaques with recombinant full-length SIV Gag p55 plus p55 affinity-purified immunoglobulin G (p55 Gag/p55-IgG) led to the generation of markedly higher frequencies of p11CM specific precursor cytotoxic T lymphocytes (p-CTLs) compared with restimulation with (i) SIV Gag p55 alone or (ii) optimal concentrations of the p11CM peptide alone. These results, along with the finding that CD4 depletion abrogated the enhancement, suggest a prominent role for CD4 ؉ T cells. Testing for p-CTLs against other Mamu-A01-restricted SIV Gag epitopes suggested that this mechanism favored recognition of the dominant p11CM peptide, potentially further skewing of the CTL response. The p-CTL enhancing effect was also decreased or abrogated by pepsin digestion of the p55-specific IgG or by the addition of monoclonal antibodies to Fc receptor (FcR) II/III, suggesting that the effect was dependent on FcR-mediated uptake of the immune-complexed antigen. Finally, incubation of antigen-presenting cells with SIV Gag p55 immune complexes in the presence of lactacystin or of bafilomycin indicated that the mechanism of antibody-mediated enhancement of cross presentation required both the proteasomal and the endosomal pathways. These data demonstrate for the first time the cross presentation of antigens via immune complexes in lentiviral infection and indicate a heretofore-unrecognized role for antibodies in modulating the magnitude and potentially also the breadth of MHC class I-restricted antigen processing and presentation and CTL responses.

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Generation of CD4+ and CD8+ T Lymphocyte Responses by Dendritic Cells Armed with PSA/Anti-PSA (Antigen/Antibody) Complexes

Cited by 61 publications

References 25 publications

Identification of HLA-DRB1*1501–Restricted T-cell Epitopes from Prostate-Specific Antigen

Identification of HLA-DRB1*1501–Restricted T-cell Epitopes from Prostate-Specific Antigen

Antibody-Mediated Immunomodulation: a Strategy To Improve Host Responses against Microbial Antigens

Evidence for Antibody-Mediated Enhancement of Simian Immunodeficiency Virus (SIV) Gag Antigen Processing and Cross Presentation in SIV-Infected Rhesus Macaques

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