HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice

Pascolo, Steve; Bervas, Nathalie; Ure, Jan; Smith, Austin; Lefrère, François; Pérarnau, Béatrice

doi:10.1084/jem.185.12.2043

Cited by 453 publications

(483 citation statements)

References 42 publications

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“…We next looked for potential T-cell epitopes of MAGE-A8, utilising the HHD system. It was shown that HHD mice selected the same immunodominant CTL epitopes as recognised by PBL in influenza-infected HLA-A2.1 individuals (Pascolo et al, 1997). Unlike traditional HLA transgenic mice, HHD mice T-cell response is HLA-A2.1 restricted, with no murine background.…”

Section: Discussionmentioning

confidence: 99%

“…The derivation of HLA-A2.1/D b -b2 monochain, transgenic, H-2D b Â b2 m double-knockout mice (HHD mice) has been described by Pascolo et al (1997). Mice were bred in the Weizmann Institute of Science (Rehovot, Israel) and maintained and treated according to NIH guidelines.…”

Section: Micementioning

confidence: 99%

“…HHD mice, a combination of classical HLA transgenesis and selective destruction of murine H-2, are D b Â b2-microglobulin (b2M) null mice, transgenic for a modified HLA-A2.1-b2-microglobulin single chain (Pascolo et al, 1997). It was demonstrated that HHD mice selected the same immunodominant CTL epitopes recognised by PBL in influenza-infected HLA-A2.1 individuals, and, unlike traditional HLA transgenic mice, there is no murine background response (Pascolo et al, 1997). Hence, these mice are a useful tool for the identification and characterisation of potential tumour-derived, HLA-A2.1 restricted, CTL epitopes.…”

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confidence: 99%

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MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

et al. 2004

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Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-arraybased differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.

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Section: Discussionmentioning

confidence: 99%

Section: Micementioning

confidence: 99%

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confidence: 99%

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MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

et al. 2004

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“…Pathogen-free 8-to 10-week-old female HLA-A2.1 transgenic HHD-1 mice 29 were housed at MannKind Corporation according to IACUC guidelines. All animal studies were reviewed and approved by an IACUC institutional review committee.…”

Section: Mouse Strains and Cell Linesmentioning

confidence: 99%

Multivalent immunity targeting tumor-associated antigens by intra-lymph node DNA-prime, peptide-boost vaccination

et al. 2010

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Active immunotherapy of cancer has yet to yield effective therapies in the clinic. To evaluate the translatability of DNA-based vaccines we analyzed the profile of T-cell immunity by plasmid vaccination in a murine model, using transcriptome microarray analysis and flow cytometry. DNA vaccination resulted in specific T cells expressing low levels of co-inhibitory molecules (most notably PD-1), strikingly different from the expression profile elicited by peptide immunization. In addition, the T-cell response primed through this dual-antigen-expressing plasmid (MART-1/Melan-A and tyrosinase) translated into a substantial proliferation capacity and functional conversion to antitumor effector cells after tyrosinase and MART-1/Melan-A peptide analog boost. Furthermore, peptide boost rescued the immune response against the subdominant tyrosinase epitope. This immunization approach could be adapted to elicit potent immunity against multiple tumor antigens, resulting in a broader immune response that was more effective in targeting human tumor cells. Finally, this study sheds light on a novel mechanism of immune homeostasis through synchronous regulation of co-inhibitory molecules on T cells, highly relevant to heterologous prime boost approaches involving DNA vaccines as priming agents.

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“…The derivation of HLA-A2.1/D b -b2 monochain, transgenic, H-2D b xb2m double-knockout mice (named HHD mice) has been described by Pascolo et al (1997). CD1-nude mice were bred in the Weizmann Institute of Science (Rehovot, Israel).…”

Section: Micementioning

confidence: 99%

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

et al. 2007

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D bÀ/À xb2 microglobulin (b2m) null mice transgenic for a chimeric HLA-A2.1/D b -b2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and to screen for putative unknown novel peptides. We utilised HHD lymphocytes to identify immunodominant epitopes of colon carcinoma overexpressed genes. We screened with HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon carcinoma overexpressed genes. This procedure culminated in the identification of seven immunogenic peptides, three of these were derived from the 'human 1-8D gene from interferon inducible gene' (1-8D). The 1-8D gene was shown to be overexpressed in fresh tumour samples. The three 1-8D peptides were both antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro and retard its growth in vivo. One of the peptides shared by all the 1-8 gene family primed efficiently normal human cytotoxic T lymphocyte precursors. These results highlight the 1-8D gene and its homologues as putative immunodominant tumour-associated antigens of colon carcinoma.

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HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice

Cited by 453 publications

References 42 publications

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

Multivalent immunity targeting tumor-associated antigens by intra-lymph node DNA-prime, peptide-boost vaccination

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

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