Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity
The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturb...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/38358 |
| _version_ | 1811253097115156480 |
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| author | William S DeWitt III Anajane Smith Gary Schoch John A Hansen Frederick A Matsen IV Philip Bradley |
| author_facet | William S DeWitt III Anajane Smith Gary Schoch John A Hansen Frederick A Matsen IV Philip Bradley |
| author_sort | William S DeWitt III |
| collection | DOAJ |
| description | The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity. |
| first_indexed | 2024-04-12T16:45:38Z |
| format | Article |
| id | doaj.art-ea01accb19154c68820bffc0cb1efcbb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:45:38Z |
| publishDate | 2018-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ea01accb19154c68820bffc0cb1efcbb2022-12-22T03:24:36ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.38358Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificityWilliam S DeWitt III0https://orcid.org/0000-0002-6802-9139Anajane Smith1Gary Schoch2John A Hansen3Frederick A Matsen IV4https://orcid.org/0000-0003-0607-6025Philip Bradley5https://orcid.org/0000-0002-0224-6464Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Department of Genome Sciences, University of Washington, Seattle, United StatesClinical Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesClinical Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesClinical Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Department of Medicine, University of Washington, Seattle, United StatesPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Department of Genome Sciences, University of Washington, Seattle, United StatesPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United StatesThe T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity.https://elifesciences.org/articles/38358adaptive immunityT cell repertoiresT cell receptor sequencing |
| spellingShingle | William S DeWitt III Anajane Smith Gary Schoch John A Hansen Frederick A Matsen IV Philip Bradley Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity eLife adaptive immunity T cell repertoires T cell receptor sequencing |
| title | Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity |
| title_full | Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity |
| title_fullStr | Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity |
| title_full_unstemmed | Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity |
| title_short | Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity |
| title_sort | human t cell receptor occurrence patterns encode immune history genetic background and receptor specificity |
| topic | adaptive immunity T cell repertoires T cell receptor sequencing |
| url | https://elifesciences.org/articles/38358 |
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