Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire
Abstract
An individual's T cell repertoire dynamically encodes their pathogen exposure history. To determine whether pathogen exposure signatures can be identified by documenting public T cell receptors (TCRs), we profiled the T cell repertoire of 666 subjects with known cytomegalovirus (CMV) serostatus by immunosequencing. We developed a statistical classification framework that could diagnose CMV status from the resulting catalog of TCRβ sequences with high specificity and sensitivity in both the original cohort and a validation cohort of 120 different subjects. We also confirmed that three of the identified CMV-associated TCRβ molecules bind CMV in vitro, and, moreover, we used this approach to accurately predict the HLA-A and HLA-B alleles of most subjects in the first cohort. As all memory T cell responses are encoded in the common format of somatic TCR recombination, our approach could potentially be generalized to a wide variety of disease states, as well as other immunological phenotypes, as a highly parallelizable diagnostic strategy.
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Immune repertoire classification typically requires extracting few patterns from a large set of sequences that are indicative for the respective immune status.
“Immune repertoire classification (Emerson et al., 2017) typically requires to extract few patterns from a large set of sequences, the repertoire, that are indicative for the respective immune status.”
From Hopfield Networks is All You Need (2020) · cites this paper as Emerson et al., 2017
Cites
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Multiple early factors anticipate post-acute COVID-19 sequelae
Su, Y., Yuan, D., Chen, D. G., Ng, R. H., Wang, K., Choi, J., Li, S., Hong, S., Zhang, R., Xie, J., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.014 · Cited by 1,156 · see citing works
Self-citationHopfield Networks is All You Need
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- Authors
- Emerson, R. O., DeWitt, W. S., Vignali, M., Gravley, J., Hu, J. K., Osborne, E. J., Desmarais, C., Klinger, M., Carlson, C. S., Hansen, J. A., Rieder, M., & Robins, H. S.
- Affiliations
- Adaptive Biotechnologies (United States) (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Emerson, Ryan O
- ORCID
- Venue
- Nature Genetics
- Published
- 2017-04-03
- Volume
- 49
- Issue
- 5
- Pages
- 659-665
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2605177850
- Cited by
- 532
- References
- 1
- Citations by year
- 2026: 59 · 2025: 75 · 2024: 58 · 2023: 66 · 2022: 68 · 2021: 68 · 2020: 49 · 2019: 43 · 2018: 38 · 2017: 8
- FWCI
- 17.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- W. M. Keck Foundation
- Adaptive Biotechnologies
- Fondation pour la Recherche Médicale
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- cytomegalovirus, T cell receptor beta chain, T cell receptor repertoire, HLA typing, memory T cells
- MeSH terms
- Algorithms, Cytomegalovirus, Histocompatibility Testing, HLA Antigens, Humans, Receptors, Antigen, T-Cell, T-Lymphocytes, Reproducibility of Results, HLA-A Antigens, HLA-B Antigens, Cohort Studies, Models, Immunological, Epitopes, T-Lymphocyte, Host-Pathogen Interactions, High-Throughput Nucleotide Sequencing
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