Type 1 diabetes-associated HLA-DQ8 transdimer accommodates a unique peptide repertoire.
J Biol Chem
; 287(12): 9514-24, 2012 Mar 16.
Article
en En
| MEDLINE
| ID: mdl-22184118
ABSTRACT
HLA-DQ2 and HLA-DQ8 are strongly predisposing haplotypes for type 1 diabetes (T1D). Yet HLA-DQ2/8 heterozygous individuals have a synergistically increased risk compared with HLA-DQ2 or HLA-DQ8 homozygote subjects that may result from the presence of a transdimer formed between the α-chain of HLA-DQ2 (DQA1*0501) and the ß-chain of HLA-DQ8 (DQB1*0302). We generated cells exclusively expressing this transdimer (HLA-DQ8trans), characterized its peptide binding repertoire, and defined a unique transdimer-specific peptide binding motif that was found to be distinct from those of HLA-DQ2 and HLA-DQ8. This motif predicts an array of peptides of islet autoantigens as candidate T cell epitopes, many of which selectively bind to the HLA transdimer, whereas others bind to both HLA-DQ8 and transdimer with similar affinity. Our findings provide a molecular basis for the association between HLA-DQ transdimers and T1D and set the stage for rational testing of potential diabetogenic peptide epitopes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Antígenos HLA-DQ
/
Diabetes Mellitus Tipo 1
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2012
Tipo del documento:
Article
País de afiliación:
Países Bajos