Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells
CD4+ T cells play a critical role in antitumor immunity via recognition of peptide antigens presented on MHC class II (MHC-II). Although some solid cancers can be induced to express MHC-II, the extent to which this enables direct recognition by tumor-specific CD4+ T cells is unclear. We isolated and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-01-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.165570 |
| _version_ | 1827768007066124288 |
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| author | Spencer E. Brightman Martin S. Naradikian Rukman R. Thota Angelica Becker Leslie Montero Milad Bahmanof Ashmitaa Logandha Ramamoorthy Premlal Jason A. Greenbaum Bjoern Peters Ezra E.W. Cohen Aaron M. Miller Stephen P. Schoenberger |
| author_facet | Spencer E. Brightman Martin S. Naradikian Rukman R. Thota Angelica Becker Leslie Montero Milad Bahmanof Ashmitaa Logandha Ramamoorthy Premlal Jason A. Greenbaum Bjoern Peters Ezra E.W. Cohen Aaron M. Miller Stephen P. Schoenberger |
| author_sort | Spencer E. Brightman |
| collection | DOAJ |
| description | CD4+ T cells play a critical role in antitumor immunity via recognition of peptide antigens presented on MHC class II (MHC-II). Although some solid cancers can be induced to express MHC-II, the extent to which this enables direct recognition by tumor-specific CD4+ T cells is unclear. We isolated and characterized T cell antigen receptors (TCRs) from naturally primed CD4+ T cells specific for 2 oncoproteins, HPV-16 E6 and the activating KRASG12V mutation, from patients with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma, respectively, and determined their ability to recognize autologous or human leukocyte antigen–matched antigen-expressing tumor cells. We found in both cases that the TCRs were capable of recognizing peptide-loaded target cells expressing the relevant MHC-II or B cell antigen-presenting cells (APCs) when the antigens were endogenously expressed and directed to the endosomal pathway but failed to recognize tumor cells expressing the source protein even after induction of surface MHC-II expression by IFN-γ or transduction with CIITA. These results suggest that priming and functional recognition of both a nuclear (E6) and a membrane-associated (KRAS) oncoprotein are predominantly confined to crosspresenting APCs rather than via direct recognition of tumor cells induced to express MHC-II. |
| first_indexed | 2024-03-11T12:06:24Z |
| format | Article |
| id | doaj.art-269a1b54d04f495aa248feef28743e01 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:24Z |
| publishDate | 2023-01-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-269a1b54d04f495aa248feef28743e012023-11-07T16:25:07ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-01-0182Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cellsSpencer E. BrightmanMartin S. NaradikianRukman R. ThotaAngelica BeckerLeslie MonteroMilad BahmanofAshmitaa Logandha Ramamoorthy PremlalJason A. GreenbaumBjoern PetersEzra E.W. CohenAaron M. MillerStephen P. SchoenbergerCD4+ T cells play a critical role in antitumor immunity via recognition of peptide antigens presented on MHC class II (MHC-II). Although some solid cancers can be induced to express MHC-II, the extent to which this enables direct recognition by tumor-specific CD4+ T cells is unclear. We isolated and characterized T cell antigen receptors (TCRs) from naturally primed CD4+ T cells specific for 2 oncoproteins, HPV-16 E6 and the activating KRASG12V mutation, from patients with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma, respectively, and determined their ability to recognize autologous or human leukocyte antigen–matched antigen-expressing tumor cells. We found in both cases that the TCRs were capable of recognizing peptide-loaded target cells expressing the relevant MHC-II or B cell antigen-presenting cells (APCs) when the antigens were endogenously expressed and directed to the endosomal pathway but failed to recognize tumor cells expressing the source protein even after induction of surface MHC-II expression by IFN-γ or transduction with CIITA. These results suggest that priming and functional recognition of both a nuclear (E6) and a membrane-associated (KRAS) oncoprotein are predominantly confined to crosspresenting APCs rather than via direct recognition of tumor cells induced to express MHC-II.https://doi.org/10.1172/jci.insight.165570ImmunologyOncology |
| spellingShingle | Spencer E. Brightman Martin S. Naradikian Rukman R. Thota Angelica Becker Leslie Montero Milad Bahmanof Ashmitaa Logandha Ramamoorthy Premlal Jason A. Greenbaum Bjoern Peters Ezra E.W. Cohen Aaron M. Miller Stephen P. Schoenberger Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells JCI Insight Immunology Oncology |
| title | Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells |
| title_full | Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells |
| title_fullStr | Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells |
| title_full_unstemmed | Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells |
| title_short | Tumor cells fail to present MHC-II–restricted epitopes derived from oncogenes to CD4+ T cells |
| title_sort | tumor cells fail to present mhc ii restricted epitopes derived from oncogenes to cd4 t cells |
| topic | Immunology Oncology |
| url | https://doi.org/10.1172/jci.insight.165570 |
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