title: 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.
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Emerson
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.|Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: William S
authors.identifier: http://orcid.org/0000-0002-6802-9139
authors.initials: WS
authors.lastname: DeWitt
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Marissa
authors.initials: M
authors.lastname: Vignali
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Gravley
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Joyce K
authors.initials: JK
authors.lastname: Hu
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Osborne
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Desmarais
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Klinger
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Rieder
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington, USA.|Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
mesh_terms: D000465:Algorithms; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006650:Histocompatibility Testing / Q000379:methods; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D011948:Receptors, Antigen, T-Cell