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T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids
- Source :
- Nature Immunology, 19(4). Nature Publishing Group
- Publication Year :
- 2017
-
Abstract
- The hallmark function of αβ 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.
- Subjects :
- 0301 basic medicine
T cell
T-Lymphocytes
Immunology
Antigen presentation
CD1
Receptors, Antigen, T-Cell
chemical and pharmacologic phenomena
Autoimmunity
Major histocompatibility complex
Lymphocyte Activation
Autoantigens
Antigens, CD1
03 medical and health sciences
Immune system
Antigen
medicine
Immunology and Allergy
Humans
Receptor
Glycoproteins
Antigen Presentation
biology
Chemistry
T-cell receptor
Lipids
Cell biology
030104 developmental biology
medicine.anatomical_structure
biology.protein
Subjects
Details
- ISSN :
- 15292916 and 15292908
- Volume :
- 19
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Nature immunology
- Accession number :
- edsair.doi.dedup.....53ffe214302ec436449dc781b4a6342f