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

（NZB x NZW） F1小鼠自发发生类似人类系统性红斑狼疮的自身免疫性疾病。主要组织相容性复合体（MHG）的H-2^<d/z>杂合性限制了疾病的发生，NZB株的H-2^<d>和NZW株的H-2^< z>。对自身反应性T细胞克隆的研究表明，Aα^<d> Aβ^<z>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基因的NZB。GD和NZW。GD菌株携带H-2^<g2>单倍型，由于发生在Ea亚区左侧的交叉，H-2^d和H-2^b单倍型之间存在H-2内重组。因为Ea^b是一个空等位基因，这些同源菌株不表达E分子。（NZB x NZW. h -2^d） Fl、（NZB x NZW. h） Fl的疾病严重程度比较。GD) F1和（NZB）。GD x NZW。GD) Fl小鼠的疾病严重程度受Ea连锁亚区控制，Ea^d抑制疾病。此外，（NZB x NZW）的疾病严重程度。与未处理的（NZB x NZW）相比，从（NZB x NZW） F1小鼠转移CD^<8+> T细胞的GD) F1小鼠明显受到抑制。GD) F1小鼠。为了确定疾病抑制的确切亚区，我们在Ea亚区右侧建立了新的H-2重组基因菌株，携带H-2^<d>和H-2^<b>单倍型之间的H-2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.