Tabary T, Prochnicka-Chalufour A, Cornillet P, Lehoang P, Betuel H, Cohen J H
Laboratoire d'Immunologie, Hôpital Robert-Debré, Reims.
C R Acad Sci III. 1991;313(13):599-605.
The Birdshot choroidoretinopathy (BSCR) is an ocular disease strongly associated with HLA-A29. The HLA-A29 specificity can be split using immunoelectrofocusing in two subtypes A29.1 and A29.2. BSCR susceptibility is exclusively linked to the HLA-A29.2 molecule. The sequence of HLA-A29.2 was established (EMBL X60108 and found to be identical between patients and healthy individuals. A single difference was found (H----D) 102) in the extra cellular domains between HLA-A29.2 and HLA-A29.1. The HLA-A29 sub-types shares the consensus HLA class I sequence (D102). The mutation exhibited by HLA-A29.1 (H102) is unique to that molecule. The ancestral type is thus HLA-A29.2 that confers the susceptibility to BSCR whereas HLA-A29.1 has arisen from a more recent mutation conferring resistance to BSCR. Another single amino-acid difference between HLA-A29.1 and HLA-A29.2 was found in the intracytoplasmic part of the molecule, HLA-A29.2 exhibiting the HLA-A consensus sequence whereas A29.1 shares with AW33.1 the mutation S----F321. In addition, the A29 specificity was assigned to L and Q amino-acids at position 62-63, which can interact with peptides into the binding groove. No specific T or B epitope of susceptibility could be considered involving the region of the mutation discriminating HLA-A29.2 from HLA-A29.1. The HLA-A29.1 mutation is unable to interact with the T cell receptor and did not seem to induce significant structural changes in the peptide-binding groove. Conversely, its position suggests that the A29.1 mutation might interfere with the binding of an accessory molecule, the CD8 molecule being the most likely candidate for that role.
鸟枪弹样脉络膜视网膜病变（BSCR）是一种与HLA - A29密切相关的眼部疾病。利用免疫电聚焦技术，HLA - A29特异性可分为两个亚型A29.1和A29.2。BSCR易感性仅与HLA - A29.2分子相关。HLA - A29.2的序列已确定（欧洲分子生物学实验室编号X60108），且患者与健康个体的该序列相同。在HLA - A29.2和HLA - A29.1的细胞外结构域之间发现了一个单一差异（H----D）102）。HLA - A29亚型共享一致的HLA I类序列（D102）。HLA - A29.1所表现出的突变（H102）是该分子特有的。因此，祖先类型是赋予BSCR易感性的HLA - A29.2，而HLA - A29.1则源于较新的突变，赋予对BSCR的抗性。在该分子的胞质部分还发现了HLA - A29.1和HLA - A29.2之间的另一个单氨基酸差异，HLA - A29.2表现出HLA - A一致序列，而A29.1与AW33.1共享突变S----F321。此外，A29特异性被指定为第62 - 63位的L和Q氨基酸，它们可与结合槽中的肽相互作用。未发现涉及区分HLA - A29.2与HLA - A29.1的突变区域的易感性特异性T或B表位。HLA - A29.1突变无法与T细胞受体相互作用，且似乎未在肽结合槽中引起显著的结构变化。相反，其位置表明A29.1突变可能会干扰辅助分子的结合，CD8分子最有可能扮演该角色。
