T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex.
Nat Immunol
; 16(11): 1153-61, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26437244
ABSTRACT
Central to adaptive immunity is the interaction between the αß T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR α-chain and ß-chain are overlaid with the α-chain and ß-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Receptores de Antígenos de Linfócitos T
/
Complexo Principal de Histocompatibilidade
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Austrália