Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire

RO Emerson, WS DeWitt, M Vignali, J Gravley, JK Hu… - Nature …, 2017 - nature.com
RO Emerson, WS DeWitt, M Vignali, J Gravley, JK Hu, EJ Osborne, C Desmarais, M Klinger…
Nature genetics, 2017nature.com
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 …
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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