Mechanism for MHC class II E region-linked autoimmune suppression.

(NZB X NZW)F1小鼠自发地患上类似人类系统性红斑狼疮的自身免疫性疾病。NZB的主要组织相容性复合体(MHG)、NZB的H-2^&lt；D&gt；和NZW株的H-2^&lt；Z&gt；H-2^&lt；D&gt；对自身反应性T细胞克隆的研究表明，Aα^&lt；d&gt；Aβ^&lt；z&gt；分子可能是疾病加速的候选分子。在本研究中，我们建立了H-2同源基因NZB.GD和NZW.GD菌株，携带H-2^和lt；G2&gt；单倍型，显示了H-2^d和H-2^b单倍型之间的H-2内重组，这是EA亚区左侧发生交叉的结果。因为Ea^b是零等位基因，所以这些同源菌株不表达E分子。比较(NZB x NZW.H-2^d)F1、(NZB x NZW.GD)F1和(NZB.GD x NZW.GD)F1小鼠的病情严重程度表明，病情严重程度由EA连锁的亚区控制，EA^d抑制疾病。此外，(NZB×NZW)的病情严重程度。与未处理的(NZB x NZW.GD)F1小鼠相比，(NZB x NZW.H-2&lt；d&gt；)F1小鼠的CD^&lt；8&gt；T细胞被显著抑制。为了确定确切的疾病抑制亚区，我们一直在建立新的H-2重组同源基因株，在H-2^&lt；d&gt；和位于EA亚区右侧的H-2^<b>单倍型之间进行H-2内重组。CD8^T细胞抑制疾病的机制正在研究中。

The (NZB x NZW) F1 mice spontaneously develop autoimmune disease resembling human systemic lupus erythematosus. The occurrence of disease is restricted by H-2^<d/z> heterozygosity of the major histocompatibility complex (MHG), H-2^<d> from NZB and H-2^<Z> of NZW strains. Studies on autoreactive T cell clones suggest that Aα^<d> Aβ^<z> molecules may be candidate for disease acceleration. In the present studies, we established H-2-congenic NZB.GD and NZW.GD strains carrying H-2^<g2> haplotype, showing the intra-H-2 recombination between H-2^d and H-2^b haplotype, as a result of crossing-over which occurred to the left of the Ea subregion. Because Ea^b is a null allele, these congenic strains do not express E molecules. Comparison of disease severity among (NZB x NZW.H-2^d) Fl, (NZB x NZW.GD) F1 and (NZB.GD x NZW.GD) Fl mice showed that disease severity is controlled by Ea-linked subregion and that Ea^d suppress the disease. Furthermore, the disease severity in (NZB x NZW. GD) F1 mice transferred with CD^<8+> T cells from (NZB x NZW.H-2^<d>) F1 mice was markedly suppressed, as compared with non-treated (NZB x NZW.GD) F1 mice. To identify exact subregion for disease suppression, we have been establishing new H-2 recombinant-congenic strains carrying intra-H-2 recombination between H-2^<d> and H-2^<b> haplotype to the right of Ea subregion. The mechanism for disease suppression by CD8^+ T cells is under investigation.