Kaminsky S G, Yoshida M A, Milisauskas V K, Nakamura I
Department of Pathology, School of Medicin and Biomedical Sciences, State University of New York, Buffalo 14214.
Immunogenetics. 1992;35(2):117-25. doi: 10.1007/BF00189521.
Hybrid resistance (HR) is primarily controlled by the genes of the Hemopoietic histocompatibility-1 (Hh-1) locus within the H-2 complex. HR is a consequence of the Hh-1-controlled target determinants in homozygous parental strain mice and their absence in heterozygous F1 hybrid mice. To examine the mechanism that controls the Hh-1 phenotype, three independent clones of somatic cell hybrids between parental lines EL-4 (C57BL/6 origin, H-2b) and R1 (C58 origin, H-2k) were studied. The line EL-4 is Hh-1b-positive and is subject to HR by H-2b heterozygous F1 mice, but R1 lacks the Hh-1b allele and is not susceptible to HR. Of the three hybrid clones, F263.2 is Hh-1b-positive, whereas the other two, F262.2 and F264.2, are Hh-1b-negative, as judged by these cells' capacity to compete in vivo with the grafted parental C57BL/6 bone marrow cells in the resistant (C57BL/6 x C3H)F1 mice. All three clones express the H-2b and H-2k class I antigens equally well, are susceptible to activated NK cells to the same extent, and all carry four copies of chromosome 17. However, Southern analysis reveals that clone F263.2 contains three copies of H-2b chromosome and one H-2k, whereas the other two clones carry two copies each of the parental chromosome 17. The results suggest that the relative copy number of specific alleles is the crucial determinant of the Hh-1 phenotype, and render unlikely both the gene dosage hypothesis and the trans-acting dominant suppression hypothesis to account for the noncodominant expression of the Hh-1 phenotype.
杂种抗性（HR）主要由H-2复合体中的造血组织相容性-1（Hh-1）位点的基因控制。HR是纯合亲本品系小鼠中Hh-1控制的靶标决定簇的结果，而在杂合F1杂种小鼠中则不存在。为了研究控制Hh-1表型的机制，研究了亲本品系EL-4（C57BL/6来源，H-2b）和R1（C58来源，H-2k）之间的三个独立的体细胞杂种克隆。EL-4品系是Hh-1b阳性，并且会受到H-2b杂合F1小鼠的HR作用，但R1缺乏Hh-1b等位基因，对HR不敏感。在这三个杂种克隆中，根据这些细胞在体内与抗性（C57BL/6×C3H）F1小鼠中移植的亲代C57BL/6骨髓细胞竞争的能力判断，F263.2是Hh-1b阳性，而另外两个F262.2和F264.2是Hh-1b阴性。所有三个克隆均同等程度地表达H-2b和H-2k I类抗原，对活化的NK细胞的敏感性相同，并且都携带四条17号染色体拷贝。然而，Southern分析显示克隆F263.2包含三个H-2b染色体拷贝和一个H-2k，而另外两个克隆各自携带两条亲代17号染色体拷贝。结果表明，特定等位基因的相对拷贝数是Hh-1表型的关键决定因素，并且使得基因剂量假说和反式作用显性抑制假说都不太可能解释Hh-1表型的非共显性表达。
