Wolf P R, Cook R G
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030.
J Exp Med. 1995 Feb 1;181(2):657-68. doi: 10.1084/jem.181.2.657.
Recent biochemical characterization of the T23-encoded Qa-1 molecule revealed an additional higher molecular mass species of 50 kD coprecipitated with the 48-kD Qa-1 molecule in H-2b and H-2d mouse strains. We now demonstrate that the 50-kD protein coprecipitated with Qa-1 is the class I-a antigen Ld in all H-2Ld-positive mouse strains examined. Furthers analyses of a panel of recombinants revealed that the 50-kD protein coprecipitated with Qa-1 in H-2b haplotype mouse strains is encoded or controlled by a gene centromeric to major histocompatibility complex class II I-E beta. We have designated this gene and corresponding protein product as Qsm, Qa-1 structure modifier. Both Ld and Qsm can interact with Qa-1 to form cell surface-expressed heterodimers in vivo. These Qa-1 heterodimers are not expressed in H-2k haplotype cells. The Qa-1/Ld and Qa-1/Qsm heterodimers are associated by noncovalent interactions and occur only between fully processed proteins. In addition, we show that the Qsm-encoded protein can form heterodimers with Ld as well, and that the Ld molecules participating in these interactions with Qa-1 and Qsm may be devoid of beta 2-microglobulin and/or peptide. These data represent the first demonstration that class I molecules can be expressed as heterodimers (Qa-1/Ld) on the cell surface, and map a gene (Qsm) that may potentially encode a novel class I molecule, or another protein, that associates with both Qa-1 and Ld. These interactions may enable increased levels of Qa-1 to reach the cell surface and may subsequently influence T cell recognition of Qa-1 and/or Ld molecules.
最近对T23编码的Qa-1分子进行的生化特性分析显示,在H-2b和H-2d小鼠品系中,与48-kD Qa-1分子共沉淀的还有一种分子量更高的50-kD物质。我们现在证明,在所有检测的H-2Ld阳性小鼠品系中,与Qa-1共沉淀的50-kD蛋白是I-a类抗原Ld。对一组重组体的进一步分析表明,在H-2b单倍型小鼠品系中与Qa-1共沉淀的50-kD蛋白由一个位于主要组织相容性复合体II类I-Eβ着丝粒的基因编码或控制。我们将该基因及其相应的蛋白产物命名为Qsm,即Qa-1结构修饰因子。Ld和Qsm都能在体内与Qa-1相互作用,形成细胞表面表达的异二聚体。这些Qa-1异二聚体在H-2k单倍型细胞中不表达。Qa-1/Ld和Qa-1/Qsm异二聚体通过非共价相互作用结合,且仅在完全加工的蛋白质之间出现。此外,我们还表明,Qsm编码的蛋白也能与Ld形成异二聚体,并且参与这些与Qa-1和Qsm相互作用的Ld分子可能不含β2-微球蛋白和/或肽段。这些数据首次证明I类分子可以在细胞表面以异二聚体(Qa-1/Ld)的形式表达,并定位了一个可能潜在编码新型I类分子或另一种与Qa-1和Ld都相关的蛋白的基因(Qsm)。这些相互作用可能使更多的Qa-1到达细胞表面,并随后影响T细胞对Qa-1和/或Ld分子的识别。