A molecular basis of human T cell receptor autoreactivity toward self-phospholipids.
Sci Immunol
; 2(16)2017 10 20.
Article
em En
| MEDLINE
| ID: mdl-29054999
ABSTRACT
Human T cell autoreactivity toward lipid antigens presented by CD1 proteins can manifest in numerous diseases, including psoriasis, contact hypersensitivities, and allergies. However, the molecular mechanisms for regulating T cell autoreactivity toward lipid antigens remain unclear. We determined the basis for T cell receptor (TCR) autoreactivity toward CD1b bound to self-phospholipids. The spectrum of self-antigens captured by CD1b skews toward abundant membrane phospholipids such as phosphatidylcholine and phosphatidylethanolamine. However, TCRs can specifically recognize rare phospholipids, including phosphatidylglycerol (PG). The structure of an autoreactive TCR bound to CD1b-PG shows that discrimination occurs through a marked induced fit movement of PG so that its polar head group fits snugly into the cationic cup of the TCR. Conversely, TCR binding toward ubiquitous self-phospholipids was sterically or electrostatically repelled. Accordingly, we describe a mechanism of TCR autoreactivity toward rare phospholipids and avoidance of autoreactivity to the most abundant self-phospholipids.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
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Autoantígenos
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Receptores de Antígenos de Linfócitos T
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Receptores de Antígenos de Linfócitos T alfa-beta
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article