Spies T, Bresnahan M, Strominger J L
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):8955-8. doi: 10.1073/pnas.86.22.8955.
A 600-kilobase (kb) DNA segment from the human major histocompatibility complex (MHC) class III region was isolated by extension of a previous 435-kb chromosome walk. The contiguous series of cloned overlapping cosmids contains the entire 555-kb interval between C2 in the complement gene cluster and HLA-B. This region is known to encode the tumor necrosis factors (TNFs) alpha and beta, B144, and the major heat shock protein HSP70. Moreover, a cluster of genes, BAT1-BAT5 (HLA-B-associated transcripts) has been localized in the vicinity of the genes for TNF alpha and TNF beta. An additional four genes were identified by isolation of corresponding cDNA clones with cosmid DNA probes. These genes for BAT6-BAT9 were mapped near the gene for C2 within a 120-kb region that includes a HSP70 gene pair. These results, together with complementary data from a similar recent study, indicated the presence of a minimum of 19 genes within the C2-HLA-B interval of the MHC class III region. Although the functional properties of most of these genes are yet unknown, they may be involved in some aspects of immunity. This idea is supported by the genetic mapping of the hemopoietic histocompatibility locus-1 (Hh-1) in recombinant mice between TNF alpha and H-2S, which is homologous to the complement gene cluster in humans.
通过扩展先前的435千碱基(kb)染色体步移,从人类主要组织相容性复合体(MHC)III类区域分离出一段600千碱基(kb)的DNA片段。一系列连续克隆的重叠黏粒包含补体基因簇中的C2与HLA - B之间的整个555千碱基间隔。已知该区域编码肿瘤坏死因子(TNFs)α和β、B144以及主要热休克蛋白HSP70。此外,一组基因BAT1 - BAT5(HLA - B相关转录本)已定位在TNFα和TNFβ基因附近。通过用黏粒DNA探针分离相应的cDNA克隆,又鉴定出另外四个基因。这些BAT6 - BAT9基因被定位在C2基因附近,位于一个120千碱基区域内,该区域包含一对HSP70基因。这些结果,连同近期一项类似研究的补充数据,表明在MHC III类区域的C2 - HLA - B间隔内至少存在19个基因。尽管这些基因中的大多数功能特性尚不清楚,但它们可能参与免疫的某些方面。造血组织相容性位点 - 1(Hh - 1)在重组小鼠中位于TNFα和与人类补体基因簇同源的H - 2S之间的遗传定位支持了这一观点。