Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Nature ; 612(7941): 771-777, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36477533

RESUMO

Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))1. How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8+ T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public ß-chain variable region-complementary-determining region 3ß (BV9-CDR3ß) motif2-4 from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent α-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3ß TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease.


Assuntos
Autoimunidade , Antígenos HLA-B , Peptídeos , Receptores de Antígenos de Linfócitos T , Humanos , Autoantígenos/química , Autoantígenos/imunologia , Autoantígenos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Antígenos HLA-B/imunologia , Antígenos HLA-B/metabolismo , Peptídeos/química , Peptídeos/imunologia , Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Líquido Sinovial/imunologia , Espondilite Anquilosante/imunologia , Uveíte Anterior/imunologia , Biblioteca de Peptídeos , Reações Cruzadas , Motivos de Aminoácidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA