Dipartimento di Medicina Rigenerativa, Immunologia dei Trapianti di Organi e Tessuti-Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Milan, Italy.
Hum Immunol. 2010 Jun;71(6):582-5. doi: 10.1016/j.humimm.2010.03.005. Epub 2010 Apr 3.
We report the identification of two novel human leucocyte antigen (HLA) in two Caucasian individuals. HLA-A0343 differs from A03010101 by four changes at nucleotides 411-414 (CCGG-->TGAA) and by a point mutation at position 418 (G-->C). These differences lead to two amino acid substitutions at codon 114, where arginine has changed into negatively charged glutamic acid, and at codon 116, where aspartic acid has changed into positively charged histidine. Molecular modeling showed that these changes have a profound influence on the overall charge of the F pocket of the groove, resulting in potentially important changes in the peptide repertoire. HLA-A0345 was found in a hematological female patient candidate to bone marrow transplantation. This new variant differs from HLA-A03010101 at position 845 (C-->A) encoding an amino acid change of threonine to asparagine at codon 258 located in the alpha3 domain. Molecular modeling does not suggest a substantial role of this substitutions on the interaction with beta2-microglobulin or CD8.
我们报告了在两名高加索个体中鉴定出的两种新型人类白细胞抗原（HLA）。HLA-A0343 与 A03010101 相比，在核苷酸 411-414 处有四个变化（CCGG-->TGAA），在位置 418 处有一个点突变（G-->C）。这些差异导致密码子 114 处的精氨酸发生负电荷谷氨酸取代，以及密码子 116 处的天冬氨酸发生正电荷组氨酸取代。分子建模表明，这些变化对槽的 F 口袋的整体电荷有深远的影响，导致肽库中可能发生重要的变化。HLA-A0345 存在于一名接受骨髓移植的血液病女性候选者中。该新变体与 HLA-A03010101 相比，在第 845 位（C-->A）编码氨基酸变化，第 258 位密码子的苏氨酸变为天冬酰胺，位于 alpha3 结构域中。分子建模表明，这种取代对与 beta2-微球蛋白或 CD8 的相互作用没有实质性作用。
