Journal article

Quantifiable predictive features define epitope-specific T cell receptor repertoires

Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi HO Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas

NATURE | NATURE PUBLISHING GROUP | Published : 2017

Abstract

T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 1015 (ref. 1) to as high as 1061 (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity. Here we rep..

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Awarded by OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH


Funding Acknowledgements

We would like to thank the St Jude Children's Research Hospital Animal Resource Center's staff for their support and excellent animal care. We thank G. Lennon for the help with single-cell sorting. We thank the Hartwell Center at St Jude for sequencing support. We also thank M. Morris, L. McLaren, T. H. Oguin III, W. Awad, A. Zamora, D. Boyd, X. Guo, S. Valkenburg, E. Grant, N. Bird and N. Mifsud for their help in conducting experiments and preparation of the manuscript. The work was supported by NIH grant AI107625 and ALSAC (to P.G.T.), FHCRC internal development funding to P.B., and an NHMRC Program Grant (1071916) to K.K. and N. L. L. N. L. L. is the recipient of a Sylvia and Charles Viertel Senior Medical Research Fellowship. E.B.C. is an NHMRC Peter Doherty Fellow and K.K. is an NHMRC SRF Level B Fellow. G.C.W. was the recipient of National Institute on Aging (NIA) K23 AG033113, NIA P30 AG021334, John A. Hartford Foundation's Center of Excellence in Geriatric Medicine Scholars Award, and Johns Hopkins Biology of Healthy Aging Program.