Nickerson C L, Hanson J, David C S
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
J Exp Med. 1990 Oct 1;172(4):1255-61. doi: 10.1084/jem.172.4.1255.
HLA-B27 transgenic mice in the context of various H-2 haplotypes were produced. A high expression of the HLA-B27 antigen was observed in mice homozygous for H-2b, H-2f, H-2s, H-2p, H-2r, and H-2k haplotypes. Mice of the H-2v haplotype expressed HLA-B27 at an intermediate level. Expression of HLA-B27 was minimal in mice of the H-2q and H-2d haplotypes. This was observed both on the B10 background and in DBA/2 or BALB/c mice. Only minimal expression of HLA-B27 could be detected in B10.PL (KuDd) or B10.RKDB (KkSkDdLb) mice, indicating that the low level of HLA-B27 expression maps to the H-2D gene or a very closely linked gene. Integration and transcription of the HLA-B27 gene does not appear to be different between high-expressing haplotypes and low-expressing haplotypes as determined by Southern and Northern blot analysis. However, expression of HLA-B27 on the cell surface correlated with the amount of HLA-B27 and beta 2M that could be immunoprecipitated with an anti-B27 antibody. Therefore, the association of the B27 heavy chain with endogenous beta 2M and subsequent expression on the cell surface are disrupted in mice with some class I H-2D genes. Possible mechanisms that might contribute to this defect in assembly, transport, and expression of class I molecules are discussed.
制备了处于各种H-2单倍型背景下的HLA - B27转基因小鼠。在H-2b、H-2f、H-2s、H-2p、H-2r和H-2k单倍型的纯合小鼠中观察到HLA - B27抗原的高表达。H-2v单倍型的小鼠以中等水平表达HLA - B27。HLA - B27在H-2q和H-2d单倍型的小鼠中表达极少。在B10背景以及DBA/2或BALB/c小鼠中均观察到这种情况。在B10.PL(KuDd)或B10.RKDB(KkSkDdLb)小鼠中仅能检测到HLA - B27的极少表达,这表明HLA - B27低水平表达定位于H-2D基因或一个紧密连锁的基因。通过Southern和Northern印迹分析确定,HLA - B27基因的整合和转录在高表达单倍型和低表达单倍型之间似乎没有差异。然而,HLA - B27在细胞表面的表达与可用抗B27抗体免疫沉淀的HLA - B27和β2M的量相关。因此,在具有某些I类H-2D基因的小鼠中,B27重链与内源性β2M的缔合以及随后在细胞表面的表达受到破坏。讨论了可能导致I类分子组装、运输和表达缺陷的潜在机制。