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T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.
Wun, Kwok S; Reijneveld, Josephine F; Cheng, Tan-Yun; Ladell, Kristin; Uldrich, Adam P; Le Nours, Jérôme; Miners, Kelly L; McLaren, James E; Grant, Emma J; Haigh, Oscar L; Watkins, Thomas S; Suliman, Sara; Iwany, Sarah; Jimenez, Judith; Calderon, Roger; Tamara, Kattya L; Leon, Segundo R; Murray, Megan B; Mayfield, Jacob A; Altman, John D; Purcell, Anthony W; Miles, John J; Godfrey, Dale I; Gras, Stephanie; Price, David A; Van Rhijn, Ildiko; Moody, D Branch; Rossjohn, Jamie.
Afiliación
  • Wun KS; Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Reijneveld JF; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
  • Cheng TY; Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
  • Ladell K; Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, MA, USA.
  • Uldrich AP; Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, MA, USA.
  • Le Nours J; Division of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
  • Miners KL; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
  • McLaren JE; ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria, Australia.
  • Grant EJ; Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Haigh OL; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
  • Watkins TS; Division of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
  • Suliman S; Division of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
  • Iwany S; Division of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
  • Jimenez J; QIMR Berghofer Medical Research Institute, Herston, Australia.
  • Calderon R; Centre for Biodiscovery and Molecular Development of Therapeutics and Centre for Biosecurity and Tropical Infectious Diseases Australian Institute of Tropical Health and Medicine, James Cook University, Cairn, Australia.
  • Tamara KL; Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, MA, USA.
  • Leon SR; Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, MA, USA.
  • Murray MB; Socios en Salud Sucursal Peru, Lima, Peru.
  • Mayfield JA; Socios en Salud Sucursal Peru, Lima, Peru.
  • Altman JD; Socios en Salud Sucursal Peru, Lima, Peru.
  • Purcell AW; Socios en Salud Sucursal Peru, Lima, Peru.
  • Miles JJ; Department of Global Health and Social Medicine, and Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Godfrey DI; Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, MA, USA.
  • Gras S; Emory University School of Medicine, Atlanta, GA, USA.
  • Price DA; Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Van Rhijn I; Centre for Biodiscovery and Molecular Development of Therapeutics and Centre for Biosecurity and Tropical Infectious Diseases Australian Institute of Tropical Health and Medicine, James Cook University, Cairn, Australia.
  • Moody DB; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
  • Rossjohn J; ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria, Australia.
Nat Immunol ; 19(4): 397-406, 2018 04.
Article en En | MEDLINE | ID: mdl-29531339
The hallmark function of αß T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Autoantígenos / Glicoproteínas / Receptores de Antígenos de Linfocitos T / Linfocitos T / Autoinmunidad / Antígenos CD1 Límite: Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Autoantígenos / Glicoproteínas / Receptores de Antígenos de Linfocitos T / Linfocitos T / Autoinmunidad / Antígenos CD1 Límite: Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Australia