Department of Cell Biology and Development, Sapienza University of Rome, 00185 Roma, Italy.
Clin Immunol. 2010 Jun;135(3):476-82. doi: 10.1016/j.clim.2010.01.009. Epub 2010 Feb 18.
HLA-B2709 does not predispose for Ankylosing Spondylitis although it differs from B2705, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp. Therefore, a productive approach to elucidate the molecular mechanisms of the disease could be the comparison of these alleles. B2705 has been shown to display certain self-peptides enriched in basic residues i.e., pVIPR and pGR, in a dual conformation and this is accompanied by the presence of specific cytotoxic T cells in patients with AS. In this study, we convalidate our previous observation that B2709 healthy subjects do not possess primary reactivity towards pVIPR while showing a prompt CD8+ T cell response driven by pGR. Notably, in the B2709 context of presentation, pVIPR assumes only a single conformation in contrast with pGR which is dimorphic. These results suggest a possible general connection between the occurrence of double peptide conformation and the property of inducing specific autoimmune responses.
HLA-B2709 尽管与在不同族群中最常见且与 AS 相关的亚型 B2705 不同，仅在 His116Asp 取代上有所不同，但它并不导致强直性脊柱炎。因此，阐明疾病分子机制的有效方法可能是比较这些等位基因。已经显示 B2705 显示某些富含碱性残基的自身肽，即 pVIPR 和 pGR，呈双重构象，并且这伴随着 AS 患者中存在特定的细胞毒性 T 细胞。在这项研究中，我们验证了我们之前的观察结果，即 B2709 健康受试者对 pVIPR 没有原发性反应，而对 pGR 表现出迅速的 CD8+T 细胞反应。值得注意的是，在 pVIPR 的呈递中，pVIPR 仅呈现一种构象，而 pGR 则呈二态性。这些结果表明，双肽构象的发生与诱导特定自身免疫反应的特性之间可能存在一般联系。
