Unaltered Class II Histocompatibility Antigens and Pathogenesis of IDDM in BB Rats-猫眼课题宝

BB 大鼠中未改变的 II 类组织相容性抗原与 IDDM 的发病机制

DOI：

10.2337/diab.38.2.267

发表时间：

1989

期刊：

Diabetes

影响因子：

7.7

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

E. Holowachuk;M. Greer

BB大鼠自发地发展为胰岛素依赖型糖尿病(IDDM)，这是一种涉及主要组织相容性复合体(MHC)II类分子的自身免疫异常。大鼠MHC(rt1复合体)编码两个II类基因座rt1.B和rt1.d。通过测定糖尿病易患(DP)BB大鼠、糖尿病抵抗(DR)BB大鼠、正常组织相容Wistar-Furth(WF)大鼠和Lewis大鼠的II类mRNAs和/或cDNA的核苷酸序列，直接研究了II类MHC分子变异或独特与IDDM易感性相关的可能性。序列分析表明，来自DP-BB、DR-BB和WF大鼠的u单倍型RT1.B和RT1.D分子的β链是相同的，但它们与已发表的大鼠等位基因和已发表的小鼠II类序列不同。在核苷酸水平上，BB和WF大鼠RTI.Dp的NH2末端结构域通过单个沉默的核苷酸替换而不同。与Lewis大鼠的序列比较表明，高变量等位基因存在差异，u和/或单倍型非常相似。这些发现表明，DP-BB大鼠的II类分子不是变异的或独特的，u单倍型的未改变的II类分子支持BB大鼠的自身免疫反应。

The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) as an autoimmune abnormality involving the class II molecules of the major histocompatibility complex (MHC). The rat MHC (RT1 complex) encodes two class II loci, RT1 .B and RT1.D. The possibility that variant or unique class II MHC molecules may be associated with IDDM susceptibility was directly examined by determining the nucleotide sequences of class II mRNAs and/or cDNAs from the diabetes-prone (DP) BB rat, the diabetes-resistant (DR) BB rat, the normal histocompatible Wistar-Furth (WF) rat, and the Lewis rat. Sequence analysis indicates that the β-chains of the RT1.B and RT1.D molecules of the u haplotype from DP-BB, DR-BB, and WF rats are identical but that they are different fromother rat alleles and published mouse class II sequences. At the nucleotide level, the NH2-terminal domain of RTI.Dp of the BB and WF rats differs by a single silent nucleotide substitution. Comparisons with the sequences of the Lewis rat indicate hypervariable allelic differences and that the u and / haplotypes are remarkably similar. These findings establish that the class II molecules of the DP-BB rat are not variant or unique and that unaltered class II molecules of the u haplotype support the autoimmune response in the BB rat.