Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens
Summary: A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two dominant viral epitopes: pp65495–503 (NLV) of cyto...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717304497 |
| _version_ | 1811227717312446464 |
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| author | Guobing Chen Xinbo Yang Annette Ko Xiaoping Sun Mingming Gao Yongqing Zhang Alvin Shi Roy A. Mariuzza Nan-ping Weng |
| author_facet | Guobing Chen Xinbo Yang Annette Ko Xiaoping Sun Mingming Gao Yongqing Zhang Alvin Shi Roy A. Mariuzza Nan-ping Weng |
| author_sort | Guobing Chen |
| collection | DOAJ |
| description | Summary: A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two dominant viral epitopes: pp65495–503 (NLV) of cytomegalovirus and M158–66 (GIL) of influenza A virus. The highly individualized repertoires (87–5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3α/CDR3β pairings. Structures of two GIL-specific TCRs bound to GIL–HLA-A2 provided a potential explanation for the lower diversity of GIL-specific versus NLV-specific repertoires. These anti-viral TCRs occupied up to 3.4% of the CD8+ TCRβ repertoire, ensuring broad T cell responses to single epitopes. Our portrait of two anti-viral TCR repertoires may inform the development of predictors of immune protection. : CD8+ T cells are essential for controlling viral infections. Chen et al. analyzed human TCR repertoires specific for two viral epitopes. Repertoire diversity was much greater than previously appreciated for both public and private TCRs. Such diversity assures protection from virus escape and the provision of T cell functional heterogeneity. Keywords: αβ TCRs for IAV-GIL, αβ TCRs for CMV-NLV, TCR repertoire, TCR-pMHC structure, CD8 T cells, human |
| first_indexed | 2024-04-12T09:46:25Z |
| format | Article |
| id | doaj.art-376bc7f7e0154f67bce4914b17bff2f6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T09:46:25Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-376bc7f7e0154f67bce4914b17bff2f62022-12-22T03:37:56ZengElsevierCell Reports2211-12472017-04-01193569583Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral AntigensGuobing Chen0Xinbo Yang1Annette Ko2Xiaoping Sun3Mingming Gao4Yongqing Zhang5Alvin Shi6Roy A. Mariuzza7Nan-ping Weng8Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USAW.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USALaboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USALaboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USAW.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USALaboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USALaboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USAW.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USALaboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, MD 21224, USA; Corresponding authorSummary: A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two dominant viral epitopes: pp65495–503 (NLV) of cytomegalovirus and M158–66 (GIL) of influenza A virus. The highly individualized repertoires (87–5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3α/CDR3β pairings. Structures of two GIL-specific TCRs bound to GIL–HLA-A2 provided a potential explanation for the lower diversity of GIL-specific versus NLV-specific repertoires. These anti-viral TCRs occupied up to 3.4% of the CD8+ TCRβ repertoire, ensuring broad T cell responses to single epitopes. Our portrait of two anti-viral TCR repertoires may inform the development of predictors of immune protection. : CD8+ T cells are essential for controlling viral infections. Chen et al. analyzed human TCR repertoires specific for two viral epitopes. Repertoire diversity was much greater than previously appreciated for both public and private TCRs. Such diversity assures protection from virus escape and the provision of T cell functional heterogeneity. Keywords: αβ TCRs for IAV-GIL, αβ TCRs for CMV-NLV, TCR repertoire, TCR-pMHC structure, CD8 T cells, humanhttp://www.sciencedirect.com/science/article/pii/S2211124717304497 |
| spellingShingle | Guobing Chen Xinbo Yang Annette Ko Xiaoping Sun Mingming Gao Yongqing Zhang Alvin Shi Roy A. Mariuzza Nan-ping Weng Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens Cell Reports |
| title | Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens |
| title_full | Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens |
| title_fullStr | Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens |
| title_full_unstemmed | Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens |
| title_short | Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens |
| title_sort | sequence and structural analyses reveal distinct and highly diverse human cd8 tcr repertoires to immunodominant viral antigens |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717304497 |
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