The insulin A-chain epitope recognized by human T cells is posttranslationally modified.
J Exp Med
; 202(9): 1191-7, 2005 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-16260488
ABSTRACT
The autoimmune process that destroys the insulin-producing pancreatic beta cells in type 1 diabetes (T1D) is targeted at insulin and its precursor, proinsulin. T cells that recognize the proximal A-chain of human insulin were identified recently in the pancreatic lymph nodes of subjects who had T1D. To investigate the specificity of proinsulin-specific T cells in T1D, we isolated human CD4(+) T cell clones to proinsulin from the blood of a donor who had T1D. The clones recognized a naturally processed, HLA DR4-restricted epitope within the first 13 amino acids of the A-chain (A1-13) of human insulin. T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. CD4(+) T cell clones that recognized this epitope were isolated from an HLA DR4(+) child with autoantibodies to insulin, and therefore, at risk for T1D, but not from two healthy HLA DR4(+) donors. We define for the first time a novel posttranslational modification that is required for T cell recognition of the insulin A-chain in T1D.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Processamento de Proteína Pós-Traducional
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Epitopos de Linfócito T
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Subunidades Proteicas
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Insulina
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article