Disease relevance of Hh1

• Resistance of H-2 heterozygous mice to parental tumors. II. Characterization of Hh-1 controlled hybrid resistance to syngeneic fibrosarcomas and the EL-4 lymphoma [1].

High impact information on Hh1

• Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant in marrow graft rejection are inherited in a recessive pattern [2].
• 5E6 is a cell surface molecule expressed on a subpopulation of murine natural killer (NK) cells that are involved in the specific rejection of H-2d or H-2f (hemopoietic histocompatibility determinant 2) bone marrow cell grafts [3].
• This finding is not easily explained by the missing self and hemopoietic histocompatibility (Hh) models for NK recognition, and has led to the idea that certain alloantigens may trigger NK cell reactivity [4].
• NK cells appear to recognize Hemopoietic histocompatibility (Hh) antigens on H-2 homozygous stem cells [5].
• We conclude that both class I (K and D) and class II (I-A and I-E) major histocompatibility complex genes, rather than hypothetical hemopoietic histocompatibility genes control hemopoietic resistance [6].

Chemical compound and disease context of Hh1

• Therefore, we examined the effect of tunicamycin (TM), an inhibitor of asparagine-linked glycosylation and ganglioside biosynthesis, on the expression of Hh-1 determinants in H-2b/Hh-1b lymphomas [7].

Biological context of Hh1

• The structural gene for the f haplotype is centromeric of Eb and may be Kf, based on recent data supporting the role of class I antigens in Hh antigen expression [8].
• Natural resistance to bone marrow stem cell (BMC) grafts in lethally irradiated mice is a consequence of natural killer cell recognition and elimination of BMC that express hemopoietic histocompatibility (Hh) antigens inherited noncodominantly [8].
• 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 [9].
• 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 [9].
• Two types of fully allogeneic donors were selected based on the expression (BALB/c), or lack of expression (DBA/1), of hybrid hematopoietic histocompatibility (Hh1) antigens [10].

Anatomical context of Hh1

• H-2 homozygosity is required for optimal immunogenicity of bone marrow cell (BMC) grafts, and "hybrid resistance" to grafts of parental strain BMC by irradiated H-2 heterozygous F1 hybrid mice suggests that Hh-1 antigens are inherited recessively [11].
• The Hh-1 antigens are also expressed on other normal hematopoietic cells and lymphoid tumors, and natural killer cells are the effectors which mediate the elimination of BMC grafts in an Hh-specific manner [11].
• In contrast, DBA/1 donor cells that were not Hh1-disparate were rejected by cells expressing Ly-1, but not NK1.1 (T cells only) [12].
• We conclude that Hh-1b is the common antigen present in EL-4 and YAC-1 cells, because B6D2F1 anti-B6 (anti-Hh-1b) cytotoxic T lymphocytes lysed both the tumor cells [13].
• The data on tumor cell proliferation in spleens and liver of lethally irradiated mice were similar to previous findings on hemopoietic histocompatibility-incompatible lymphomas [14].

Associations of Hh1 with chemical compounds

• The nature of hemopoietic histocompatibility determinants. Differential sensitivity of Hh-1b and H-2b determinants to tunicamycin [7].
• In the second step, asialo GM1-positive natural killer cells stimulated by IFN-alpha/beta recognize Hh antigens on marrow stem cells and cause rejection [15].
• Treatment of the recipient with cyclophosphamide 2 days following allogeneic bone marrow transplantation reduced the dose of radiation sufficient for reliable engraftment to only 500 cGy of total body irradiation, regardless of MHC and Hh-1 disparity [16].

Regulatory relationships of Hh1

• Studies further showed that BALB/c donor cells exhibiting an Hh1 disparity were rejected by host cells expressing NK1.1 or Ly-1 (NK cells and T cells) [12].

Other interactions of Hh1

• Our data suggest that Hh-1b antigen is recognized by both types of NK cells, but that additional determinants must be present on YAC-1 cells [13].

Analytical, diagnostic and therapeutic context of Hh1

• These studies provide definitive data that CD3+ cells participate in the rejection of either Hh1+ or Hh1null T cell-depleted allografts and offer new strategies for alloengraftment using regimens containing nonmitogenic anti-CD3 [12].
• Involvement of MHC-linked hemopoietic-histocompatibility genes in allogeneic bone marrow transplantation in mice [17].

References