The T cell receptor sequence influences the likelihood of T cell memory formation
Kaitlyn A. Lagattuta,
Ayano C. Kohlgruber,
Nouran S. Abdelfattah,
Aparna Nathan,
Laurie Rumker,
Michael E. Birnbaum,
Stephen J. Elledge,
Soumya Raychaudhuri
Affiliations
Kaitlyn A. Lagattuta
Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Ayano C. Kohlgruber
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; Division of Immunology, Boston Children’s Hospital, Boston, MA, USA
Nouran S. Abdelfattah
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA
Aparna Nathan
Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Laurie Rumker
Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Michael E. Birnbaum
Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
Stephen J. Elledge
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA
Soumya Raychaudhuri
Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Corresponding author
Summary: The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual’s immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells. We find that hydrophobic complementarity-determining region (CDR)3 residues promote regulatory T cell fates in both the CD8 and CD4 lineages. Most strikingly, we find a set of TCR sequence features that promote the T cell transition from naive to memory. We quantify the extent of these features through our TCR scoring function “TCR-mem.” Using TCR transduction experiments, we demonstrate that increased TCR-mem promotes T cell activation, even among T cells that recognize the same antigen. Our results reveal a common set of TCR sequence features that enable T cell activation and immunological memory.
