title: Mouse and Human CD1d-Self-Lipid Complexes Are Recognized Differently by Murine Invariant Natural Killer T Cell Receptors.
abstract: Invariant natural killer T (iNKT) cells recognize self-lipids presented by CD1d through characteristic TCRs, which mainly consist of the invariant Vα14-Jα18 TCRα chain and Vβ8.2, 7 or 2 TCRβ chains with hypervariable CDR3β sequences in mice. The iNKT cell-CD1d axis is conserved between humans and mice, and human CD1d reactivity of murine iNKT cells have been described. However, the detailed differences between the recognition of human and mouse CD1d bound to various self-lipids by mouse iNKT TCRs are largely unknown. In this study, we generated a de novo murine iNKT TCR repertoire with a wider range of autoreactivity compared with that of naturally occurring peripheral iNKT TCRs. Vβ8.2 mouse iNKT TCRs capable of recognizing the human CD1d-self-lipid tetramer were identified, although such clones were not detectable in the Vβ7 or Vβ2 iNKT TCR repertoire. In line with previously reports, clonotypic Vβ8.2 iNKT TCRs with unique CDR3β loops did not discriminate among lipids presented by mouse CD1d. Unexpectedly, however, these iNKT TCRs showed greater ligand selectivity toward human CD1d presenting the same lipids. Our findings demonstrated that the recognition of mouse and human CD1d-self-lipid complexes by murine iNKT TCRs is not conserved, thereby further elucidating the differences between cognate and cross-species reactivity of self-antigens by mouse iNKT TCRs.
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tingxi
authors.initials: T
authors.lastname: Guo
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kenji
authors.initials: K
authors.lastname: Chamoto
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Munehide
authors.initials: M
authors.lastname: Nakatsugawa
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Ochi
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Anczurowski
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Butler
authors.affiliation: Tumor Immunotherapy Program, Campbell Family Institute for Breast Cancer Research, Campbell Family Cancer Research Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Naoto
authors.initials: N
authors.lastname: Hirano
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D000070136:Lipid Droplet Associated Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; D001324:Autoantigens; D000070136:Lipid Droplet Associated Proteins; D011948:Receptors, Antigen, T-Cell