We are analyzing https://link.springer.com/article/10.1007/s00262-011-1183-3.

Title:
Endogenous retrovirus sequences as a novel class of tumor-specific antigens: an example of HERV-H env encoding strong CTL epitopes | Cancer Immunology, Immunotherapy
Description:
Our genome consists to about 8% of human endogenous retroviral (HERV) sequences. These HERVs have been discussed to be linked to human diseases for decades. Recently, a detailed analysis of a HERV-H sequence located on chromosome Xp22.3 revealed a strong expression in a subset of gastrointestinal cancers whereas expression in normal tissues and in other cancer entities was low. In the present study, we used the reverse immunology approach to test the immunological potential of this HERV-H ORF on Xp22.3. A total of ten peptides displaying HLA-A2.1-binding motifs were selected from the predicted env protein sequence. Stimulation of peripheral T cells with retroviral peptides (RVPs) presented by autologous antigen-presenting cells clearly resulted in sustained proliferation of predominantly CD8+ T cells. High numbers of IFN-γ-secreting T cells were detectable after several weekly stimulations with RVP mixes. Reactivity observed in RVP-Mix–stimulated cultures was attributable to RVP03, RVP09 and to a lower extend to RVP08, suggesting those to be highly immunogenic epitopes. Besides killing of RVP-loaded target cells, up to 40% specific lysis of colorectal carcinoma cell lines endogenously expressing this HERV-H Xp22.3 ORF was achieved. These data demonstrate that human T cells can be sensitized toward HERV peptides and moreover posses a high lytic potential toward HERV-H expressing CRC cells. Additionally, these data hint toward endogenous ENV protein expression followed by proteasomal degradation and presentation in the context of HLA molecules. Finally, our data strengthen the view that HERV-encoded sequences should be considered as a new class of tumor-specific antigens.
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Topics {✒️}

month download article/chapter family elements reactivated rvp-mix–stimulated cultures antigen-specific immune response generate autologous antigen-specific autologous antigen-presenting cells rvp-loaded target cells human endogenous retroviral human colorectal cancer endogenous retroviral sequence article cancer immunology highly immunogenic epitopes endogenous retrovirus sequences human endogenous retrovirus human endogenous retrovirus endogenous human retroelements full article pdf human endogenous retroviruses von knebel doeberitz privacy choices/manage cookies reverse immunology approach retroviral rna identified melanoma cell lines cell epitope generated expressing crc cells antigen-presenting cells mullins & michael linnebacher article mullins tumor-specific antigens european economic area ifn-γ-secreting telomerase catalytic subunit env gene expression tumor-specific cytotoxic conditions privacy policy human breast cancer human kidney cancer widely expressed tumor section molecular oncology breast cancer patients check access instant access electronic supplementary material article log related subjects retroviral peptides cd40-activated human accepting optional cookies large-scale analysis quantitative expression analyses

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      description:Our genome consists to about 8% of human endogenous retroviral (HERV) sequences. These HERVs have been discussed to be linked to human diseases for decades. Recently, a detailed analysis of a HERV-H sequence located on chromosome Xp22.3 revealed a strong expression in a subset of gastrointestinal cancers whereas expression in normal tissues and in other cancer entities was low. In the present study, we used the reverse immunology approach to test the immunological potential of this HERV-H ORF on Xp22.3. A total of ten peptides displaying HLA-A2.1-binding motifs were selected from the predicted env protein sequence. Stimulation of peripheral T cells with retroviral peptides (RVPs) presented by autologous antigen-presenting cells clearly resulted in sustained proliferation of predominantly CD8+ T cells. High numbers of IFN-γ-secreting T cells were detectable after several weekly stimulations with RVP mixes. Reactivity observed in RVP-Mix–stimulated cultures was attributable to RVP03, RVP09 and to a lower extend to RVP08, suggesting those to be highly immunogenic epitopes. Besides killing of RVP-loaded target cells, up to 40% specific lysis of colorectal carcinoma cell lines endogenously expressing this HERV-H Xp22.3 ORF was achieved. These data demonstrate that human T cells can be sensitized toward HERV peptides and moreover posses a high lytic potential toward HERV-H expressing CRC cells. Additionally, these data hint toward endogenous ENV protein expression followed by proteasomal degradation and presentation in the context of HLA molecules. Finally, our data strengthen the view that HERV-encoded sequences should be considered as a new class of tumor-specific antigens.
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