21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison's disease

作者：Rottembourg Diane; Deal Cheri; Lambert Marion; Mallone Roberto; Carel Jean Claude; Lacroix Andre; Caillat Zucman Sophie; le Deist Francoise^*

来源：Journal of Autoimmunity, 2010, 35(4): 309-315.

DOI：10.1016/j.jaut.2010.07.001

• Addison s disease
• Autoimmune polyglandular syndrome
• APECED
• Epitope mapping study
• T cell epitope
• 21 Hydroxylase

In autoimmune adrenal deficiency autoantibodies target the 21-hydroxylase (21OH) protein However it is presumed that autoreactive T cells rather than antibodies are the main effectors of adrenal gland destruction but their identification is still lacking We performed a T-cell epitope mapping study using 49 overlapping 20mer peptides covering the 21OH sequence in patients with isolated Addison s disease Autoimmune Polyendocrine Syndrome 1 and 2 IFN gamma ELISPOT responses against these peptides were stronger broader and more prevalent among patients than in controls whatever the disease presentation Five peptides elicited T-cell responses in patients only (68% sensitivity 100% specificity) Blocking experiments identified IFN gamma-producing cells as CD8 T lymphocytes with two peptides frequently recognized in HLA-B8+ patients and a third one targeted in HLA-B35+ subjects In particular the 21OH(431-450) peptide was highly immunodominant as it was recognized in more than 30% of patients all carrying the HLA-B8 restriction element This 21OH(431-450) region contained an EPLARLEL octamer (21OH(431-438)) predicted to bind to HIA-B8 with high affinity Indeed circulating EPLARLEL-specific CD8 T cells were detected at significant frequencies in HLA-B8+ patients

• 出版日期2010-12