Academic Journal
Characterization of CD8+ T-cell responses to non-anchor-type HLA class I neoantigens with single amino-acid substitutions
| العنوان: | Characterization of CD8+ T-cell responses to non-anchor-type HLA class I neoantigens with single amino-acid substitutions |
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| المؤلفون: | Tomoyo Shinkawa, Serina Tokita, Munehide Nakatsugawa, Yasuhiro Kikuchi, Takayuki Kanaseki, Toshihiko Torigoe |
| المصدر: | OncoImmunology, Vol 10, Iss 1 (2021) |
| بيانات النشر: | Taylor & Francis Group, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | tumor antigen, neoantigen, cd8+ t cells, immunogenicity, hla ligandome, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | CD8+ T cells are capable of recognizing mutation-derived neoantigens displayed by HLA class I molecules, thereby exhibiting the ability to distinguish between cancer and normal cells. However, accumulating evidence has shown that only a small fraction of nonsynonymous somatic mutations give rise to clinically relevant neoantigens. The properties of such neoantigens, which must be presented by HLA and immunogenic to induce a T-cell response, remain elusive. In this study, we explored the HLA class I ligandome of a human cancer cell line with microsatellite instability using a proteogenomic approach. The results demonstrated that neoantigens accounted for only 0.34% of the HLA class I ligandome, and most neoantigens were encoded by genes with abundant expression. Thereafter, T-cell responses were prioritized, and immunodominant neoantigens were defined using naive CD8+ T cells derived from healthy donors. AKF9, an immunogenic neoantigen with a mutation at a non-anchor position, formed a stable peptide-HLA complex. T-cell responses were analyzed against a panel of AKF9 variants with single amino-acid substitutions, in which mutations did not alter the high HLA-binding affinity and stability. The responses varied across individuals, demonstrating the impact of heterogeneous T-cell repertoires in this human cancer model. Moreover, responses were biased toward a variant group with large structural changes compared to the wild-type peptide. Thus, naive T-cell induction can be attributed to multiple determinants. Combining structural dissimilarity with gene-expression levels, HLA-binding affinity, and stability may further help prioritize the immunogenicity of non-anchor-type neoantigens. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162-402X 2162402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2020.1870062 |
| URL الوصول: | https://doaj.org/article/cd207c8fc7084b698ed44490a7e0fda9 |
| رقم الانضمام: | edsdoj.207c8fc7084b698ed44490a7e0fda9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2020.1870062 |