Hemopoietic histocompatibility (Hh-1) phenotype and the regulation of its expression.
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.
Kaminsky
S G
SG
Department of Pathology, School of Medicin and Biomedical Sciences, State University of New York, Buffalo 14214.
Yoshida
M A
MA
Milisauskas
V K
VK
Nakamura
I
I
D000818:Animals; D015139:Blotting, Southern; D002874:Chromosome Mapping; D005260:Female; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000032:analysis / Q000235:genetics; D006649:Histocompatibility Antigens / Q000235:genetics*; D006822:Hybrid Cells; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D006183:H-2 Antigens; C056907:Hh1 protein, mouse; D006649:Histocompatibility Antigens