Hydrophobic CDR3 residues promote the development of self-reactive T cells.
Nat Immunol
; 17(8): 946-55, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27348411
ABSTRACT
Studies of individual T cell antigen receptors (TCRs) have shed some light on structural features that underlie self-reactivity. However, the general rules that can be used to predict whether TCRs are self-reactive have not been fully elucidated. Here we found that the interfacial hydrophobicity of amino acids at positions 6 and 7 of the complementarity-determining region CDR3ß robustly promoted the development of self-reactive TCRs. This property was found irrespective of the member of the ß-chain variable region (Vß) family present in the TCR or the length of the CDR3ß. An index based on these findings distinguished Vß2(+), Vß6(+) and Vß8.2(+) regulatory T cells from conventional T cells and also distinguished CD4(+) T cells selected by the major histocompatibility complex (MHC) class II molecule I-A(g7) (associated with the development of type 1 diabetes in NOD mice) from those selected by a non-autoimmunity-promoting MHC class II molecule I-A(b). Our results provide a means for distinguishing normal T cell repertoires versus autoimmunity-prone T cell repertoires.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoimunidade
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Subpopulações de Linfócitos T
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Linfócitos T Reguladores
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Regiões Determinantes de Complementaridade
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Diabetes Mellitus Tipo 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article