Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses.
Antibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5464627?pdf=render |
| _version_ | 1818854996595179520 |
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| author | Marta Spodzieja Sławomir Lach Justyna Iwaszkiewicz Valérie Cesson Katarzyna Kalejta Daniel Olive Olivier Michielin Daniel E Speiser Vincent Zoete Laurent Derré Sylwia Rodziewicz-Motowidło |
| author_facet | Marta Spodzieja Sławomir Lach Justyna Iwaszkiewicz Valérie Cesson Katarzyna Kalejta Daniel Olive Olivier Michielin Daniel E Speiser Vincent Zoete Laurent Derré Sylwia Rodziewicz-Motowidło |
| author_sort | Marta Spodzieja |
| collection | DOAJ |
| description | Antibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising target for immunotherapy. Indeed, BTLA inhibits T-cell proliferation and cytokine production. The crystal structure of the BTLA/HVEM complex has shown that the HVEM(26-38) fragment is directly involved in protein binding. We designed and analyzed the capacity of several analogs of this fragment to block the ligation between BTLA and HVEM, using competitive ELISA and cellular assay. We found that the HVEM(23-39) peptide can block BTLA/HVEM ligation. However, the blocking ability was due to the Cys encompassed in this peptide and that even free cysteine targeted the BTLA protein and blocked its interaction with HVEM. These data highlight a Cys-related artefact in vitro, which should be taken in consideration for future development of BTLA/HVEM blocking compounds. |
| first_indexed | 2024-12-19T08:01:35Z |
| format | Article |
| id | doaj.art-0046835261884b61849fa0574be8c961 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T08:01:35Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0046835261884b61849fa0574be8c9612022-12-21T20:29:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017920110.1371/journal.pone.0179201Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses.Marta SpodziejaSławomir LachJustyna IwaszkiewiczValérie CessonKatarzyna KalejtaDaniel OliveOlivier MichielinDaniel E SpeiserVincent ZoeteLaurent DerréSylwia Rodziewicz-MotowidłoAntibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising target for immunotherapy. Indeed, BTLA inhibits T-cell proliferation and cytokine production. The crystal structure of the BTLA/HVEM complex has shown that the HVEM(26-38) fragment is directly involved in protein binding. We designed and analyzed the capacity of several analogs of this fragment to block the ligation between BTLA and HVEM, using competitive ELISA and cellular assay. We found that the HVEM(23-39) peptide can block BTLA/HVEM ligation. However, the blocking ability was due to the Cys encompassed in this peptide and that even free cysteine targeted the BTLA protein and blocked its interaction with HVEM. These data highlight a Cys-related artefact in vitro, which should be taken in consideration for future development of BTLA/HVEM blocking compounds.http://europepmc.org/articles/PMC5464627?pdf=render |
| spellingShingle | Marta Spodzieja Sławomir Lach Justyna Iwaszkiewicz Valérie Cesson Katarzyna Kalejta Daniel Olive Olivier Michielin Daniel E Speiser Vincent Zoete Laurent Derré Sylwia Rodziewicz-Motowidło Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. PLoS ONE |
| title | Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. |
| title_full | Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. |
| title_fullStr | Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. |
| title_full_unstemmed | Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. |
| title_short | Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. |
| title_sort | design of short peptides to block btla hvem interactions for promoting anticancer t cell responses |
| url | http://europepmc.org/articles/PMC5464627?pdf=render |
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