title: αβT cell receptors expressed by CD4(-)CD8αβ(-) intraepithelial T cells drive their fate into a unique lineage with unusual MHC reactivities.
abstract: Coreceptor CD4 and CD8αβ double-negative (DN) TCRαβ(+) intraepithelial T cells, although numerous, have been greatly overlooked and their contribution to the immune response is not known. Here we used T cell receptor (TCR) sequencing of single cells combined with retrogenic expression of TCRs to study the fate and the major histocompatibility complex (MHC) restriction of DN TCRαβ(+) intraepithelial T cells. The data show that commitment of thymic precursors to the DN TCRαβ(+) lineage is imprinted by their TCR specificity. Moreover, the TCRs they express display a diverse and unusual pattern of MHC restriction that is nonoverlapping with that of CD4(+) or CD8αβ(+) T cells, indicating that they sense antigens that are not recognized by the conventional T cell subsets. The new insights indicate that DN TCRαβ(+) T cells form a third lineage of TCRαβ T lymphocytes expressing a variable TCR repertoire, which serve nonredundant immune functions.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.|Clinical Microbiology-Immunology, NUS Building 6C, 901 85 Umeå, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mayans
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.|eBioscience, 10255 Science center drive, San Diego, CA, 92121, USA.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Stepniak
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.|HHMI - UCSD, 9500 Gilman Dr, George Palade 310 La Jolla, CA 92093-0647, USA.
authors.forename: Sakina
authors.initials: S
authors.lastname: Palida
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Larange
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dreux
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.|The Scripps Research Institute, 10550 North Torrey Pines Road, MB-209, La Jolla, CA, 92037, USA.
authors.forename: Britni
authors.initials: B
authors.lastname: Arlian
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.|Riken, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Shinnakasu
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Hilde
authors.initials: H
authors.lastname: Cheroutre
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Florence
authors.initials: F
authors.lastname: Lambolez
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007157:Immunologic Surveillance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta