T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide-MHC complexes

Amalie Kai Bentzen, Lina Such, Kamilla Kjærgaard Jensen, Andrea Marion Marquard, Leon Eyrich Jessen, Natalie J. Miller, Candice D Church, Rikke Birgitte Lyngaa, David M. Koelle, Jürgen C. Becker, Carsten Linnemann, Ton N. M. Schumacher, Paolo Marcatili, Paul Nghiem, Morten Nielsen, Sine Reker Hadrup*

*Corresponding author for this work

    Research output: Contribution to journalLetterResearchpeer-review

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    Abstract

    The promiscuous nature of T-cell receptors (TCRs) allows T cells to recognize a large variety of pathogens, but makes it challenging to understand and control T-cell recognition. Existing technologies provide limited information about the key requirements for T-cell recognition and the ability of TCRs to cross-recognize structurally related elements. Here we present a 'one-pot' strategy for determining the interactions that govern TCR recognition of peptide-major histocompatibility complex (pMHC). We measured the relative affinities of TCRs to libraries of barcoded peptide-MHC variants and applied this knowledge to understand the recognition motif, here termed the TCR fingerprint. The TCR fingerprints of 16 different TCRs were identified and used to predict and validate cross-recognized peptides from the human proteome. The identified fingerprints differed among TCRs recognizing the same epitope, demonstrating the value of this strategy for understanding T-cell interactions and assessing potential cross-recognition before selection of TCRs for clinical development.
    Original languageEnglish
    JournalNature Biotechnology
    Volume36
    Issue number12
    Pages (from-to)1191-1196
    ISSN1087-0156
    DOIs
    Publication statusPublished - 2018

    Cite this

    Bentzen, Amalie Kai ; Such, Lina ; Jensen, Kamilla Kjærgaard ; Marquard, Andrea Marion ; Jessen, Leon Eyrich ; Miller, Natalie J. ; Church, Candice D ; Lyngaa, Rikke Birgitte ; Koelle, David M. ; Becker, Jürgen C. ; Linnemann, Carsten ; Schumacher, Ton N. M. ; Marcatili, Paolo ; Nghiem, Paul ; Nielsen, Morten ; Hadrup, Sine Reker. / T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide-MHC complexes. In: Nature Biotechnology. 2018 ; Vol. 36, No. 12. pp. 1191-1196.
    @article{503732dc3655447f85d18b126f87cf4c,
    title = "T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide-MHC complexes",
    abstract = "The promiscuous nature of T-cell receptors (TCRs) allows T cells to recognize a large variety of pathogens, but makes it challenging to understand and control T-cell recognition. Existing technologies provide limited information about the key requirements for T-cell recognition and the ability of TCRs to cross-recognize structurally related elements. Here we present a 'one-pot' strategy for determining the interactions that govern TCR recognition of peptide-major histocompatibility complex (pMHC). We measured the relative affinities of TCRs to libraries of barcoded peptide-MHC variants and applied this knowledge to understand the recognition motif, here termed the TCR fingerprint. The TCR fingerprints of 16 different TCRs were identified and used to predict and validate cross-recognized peptides from the human proteome. The identified fingerprints differed among TCRs recognizing the same epitope, demonstrating the value of this strategy for understanding T-cell interactions and assessing potential cross-recognition before selection of TCRs for clinical development.",
    author = "Bentzen, {Amalie Kai} and Lina Such and Jensen, {Kamilla Kj{\ae}rgaard} and Marquard, {Andrea Marion} and Jessen, {Leon Eyrich} and Miller, {Natalie J.} and Church, {Candice D} and Lyngaa, {Rikke Birgitte} and Koelle, {David M.} and Becker, {J{\"u}rgen C.} and Carsten Linnemann and Schumacher, {Ton N. M.} and Paolo Marcatili and Paul Nghiem and Morten Nielsen and Hadrup, {Sine Reker}",
    year = "2018",
    doi = "10.1038/nbt.4303",
    language = "English",
    volume = "36",
    pages = "1191--1196",
    journal = "Nature Biotechnology",
    issn = "1087-0156",
    publisher = "Nature Publishing Group",
    number = "12",

    }

    T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide-MHC complexes. / Bentzen, Amalie Kai; Such, Lina; Jensen, Kamilla Kjærgaard; Marquard, Andrea Marion; Jessen, Leon Eyrich; Miller, Natalie J.; Church, Candice D; Lyngaa, Rikke Birgitte; Koelle, David M.; Becker, Jürgen C.; Linnemann, Carsten; Schumacher, Ton N. M.; Marcatili, Paolo; Nghiem, Paul; Nielsen, Morten; Hadrup, Sine Reker.

    In: Nature Biotechnology, Vol. 36, No. 12, 2018, p. 1191-1196.

    Research output: Contribution to journalLetterResearchpeer-review

    TY - JOUR

    T1 - T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide-MHC complexes

    AU - Bentzen, Amalie Kai

    AU - Such, Lina

    AU - Jensen, Kamilla Kjærgaard

    AU - Marquard, Andrea Marion

    AU - Jessen, Leon Eyrich

    AU - Miller, Natalie J.

    AU - Church, Candice D

    AU - Lyngaa, Rikke Birgitte

    AU - Koelle, David M.

    AU - Becker, Jürgen C.

    AU - Linnemann, Carsten

    AU - Schumacher, Ton N. M.

    AU - Marcatili, Paolo

    AU - Nghiem, Paul

    AU - Nielsen, Morten

    AU - Hadrup, Sine Reker

    PY - 2018

    Y1 - 2018

    N2 - The promiscuous nature of T-cell receptors (TCRs) allows T cells to recognize a large variety of pathogens, but makes it challenging to understand and control T-cell recognition. Existing technologies provide limited information about the key requirements for T-cell recognition and the ability of TCRs to cross-recognize structurally related elements. Here we present a 'one-pot' strategy for determining the interactions that govern TCR recognition of peptide-major histocompatibility complex (pMHC). We measured the relative affinities of TCRs to libraries of barcoded peptide-MHC variants and applied this knowledge to understand the recognition motif, here termed the TCR fingerprint. The TCR fingerprints of 16 different TCRs were identified and used to predict and validate cross-recognized peptides from the human proteome. The identified fingerprints differed among TCRs recognizing the same epitope, demonstrating the value of this strategy for understanding T-cell interactions and assessing potential cross-recognition before selection of TCRs for clinical development.

    AB - The promiscuous nature of T-cell receptors (TCRs) allows T cells to recognize a large variety of pathogens, but makes it challenging to understand and control T-cell recognition. Existing technologies provide limited information about the key requirements for T-cell recognition and the ability of TCRs to cross-recognize structurally related elements. Here we present a 'one-pot' strategy for determining the interactions that govern TCR recognition of peptide-major histocompatibility complex (pMHC). We measured the relative affinities of TCRs to libraries of barcoded peptide-MHC variants and applied this knowledge to understand the recognition motif, here termed the TCR fingerprint. The TCR fingerprints of 16 different TCRs were identified and used to predict and validate cross-recognized peptides from the human proteome. The identified fingerprints differed among TCRs recognizing the same epitope, demonstrating the value of this strategy for understanding T-cell interactions and assessing potential cross-recognition before selection of TCRs for clinical development.

    U2 - 10.1038/nbt.4303

    DO - 10.1038/nbt.4303

    M3 - Letter

    VL - 36

    SP - 1191

    EP - 1196

    JO - Nature Biotechnology

    JF - Nature Biotechnology

    SN - 1087-0156

    IS - 12

    ER -