HLA-DRB1 leprogenic motifs in nigerian population groups.
HLA-DRB1 leprogenic motifs in nigerian population groups.
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尼日利亚人群中的 HLA-DRB1 麻风基序。
DOI：
10.1046/j.1365-2249.1999.01034.x
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发表时间：
1999
影响因子：
4.6
通讯作者：
Fraser,PA
中科院分区：
文献类型：
--
作者：
Uko,GP;Lu,LY;Asuquo,MA;Fici,D;Mahan,S;Awdeh,Z;Udim,ER;Ding,W;Umana,U;Adewole,T;Fraser,PA
在尼日利亚三个麻风种族（n= 287）和170名对照组中检测了HLA-DRB 1等位基因肽结合沟中的氨基酸残基，以确定DRB 1等位基因在麻风分枝杆菌疾病结局中的作用。 检测到9个带正电荷的基序和另外两个带中性电荷的结合沟。这些基序在麻风（麻风源性）中的出现频率高于预期的偶然性（P<0.0001）。 与此相反，五个图案与净负或“修改”中性电荷的口袋呈负相关，麻风病。我们的结论是麻风分枝杆菌感染的临床结果在很大程度上是由DRB 1等位基因中的一个共同表位决定的，该表位由几个基序标记。 这些基序出现在其他正常的DRB 1等位基因中，其特征在于结合沟中的净正电荷或中性电荷。我们假设这些极性导致DRB 1与麻风分枝杆菌结合不良。 在呈递时，通过T细胞受体的信号导致减弱的细胞介导的免疫。根据麻风分枝杆菌和宿主DRB 1等位基因之间电荷一致性的程度，所产生的反应转化为各种形式的麻风。 HLA复合体内或外的其他因素，如T细胞受体库，也可能影响所产生的疾病。
Amino acid residues involved in the peptide binding groove of HLA‐DRB1 alleles were examined in three Nigerian ethnic groups with leprosy (n= 287) and 170 controls to determine the role of DRB1 alleles in disease outcome withMycobacterium leprae. Nine positively charged motifs and two others with neutral charge to the binding groove were detected. These motifs occurred more frequently in leprosy (leprogenic) than was expected by chance (P< 0.0001). In contrast, five motifs with net negative or ‘modified’ neutral charges to the pocket were negatively associated with leprosy. We conclude that clinical outcome of infection withM. lepraeis largely determined by a shared epitope in DRB1 alleles marked by several motifs. These motifs occur in otherwise normal DRB1 alleles, characterized by net positive or neutral charges in the binding groove. We hypothesize that these polarities cause poor binding of DRB1 toM. leprae. On presentation, the signal via the T cell receptor results in muted cell‐mediated immunity. The resulting response translates to various forms of leprosy depending on degree of charge consonance betweenM. lepraeand host DRB1 allele. Other factors within or without the HLA complex, such as the T cell receptor repertoire, may also influence the resulting disease.