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Gene Review

H44  -  histocompatibility 44

Mus musculus

Synonyms: H-44
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Disease relevance of H44

  • To determine the relative contribution of lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis to the pathogenesis of meningococcal sepsis, this study quantitatively compared cytokine induction by isolated LPS, wild-type serogroup B meningococci (strain H44/76), and LPS-deficient mutant meningococci (strain H44/76[pLAK33]) [1].
  • AlPO(4), Rhodobacter sphaeroides LPS, monophosphoryl lipid A and alkali-hydrolyzed meningococcal LPS showed significantly lower adjuvant activity than did H44/76 LPS [2].
  • In the present study, we have changed the fatty acid composition of Neisseria meningitidis LPS by replacing the lpxA gene of strain H44/76 with the Escherichia coli or Pseudomonas aeruginosa homologue [3].

High impact information on H44

  • This consisted of ligating a digest of total chromosomal DNA to a 1.1 kb restriction fragment containing an erythromycin-resistance marker (ermC), and subsequent transformation of the ligation mixture into the homologous meningococcal strain H44/76 [4].
  • To determine whether LPS has any effect on the B-cell-stimulatory effect of neisserial porins (essential for the adjuvant activity of neisserial porins), B cells from both murine strains were incubated with outer membrane complexes (OMCs) prepared from strain H44/76 and its LPS-negative mutant [5].
  • The peptides contain a fluorescein label and the core determinant amino acid sequence TKDTNNN (residues 180-186) of the PorA P1.16 epitope of meningococcal strain H44/76 [6].
  • Starting with a derivative of strain H44/76 deficient in class 3 outer membrane protein, a second class 1 gene was inserted into the chromosome, through homologous recombination with a suicide plasmid carrying the class 1 gene from strain 2996 placed within a class 5 gene [7].
  • Clone H44 encodes 40 consecutive glutamines, more than any other entry in the nonredundant GenBank protein database and well within the range that causes neuronal degeneration in several of the glutamine expansion diseases [8].

Biological context of H44

  • Multiplicity of chromosome 2 histocompatibility genes: new loci, H-44 and H-45 [9].
  • In this study, the protective activity of murine monoclonal PorA specific antibodies against four isogenic meningococcal P1.7,16 target strains, the prototype P1.7,16a and three loop 4 point mutation variants (designated P1.7,16b to d) constructed from reference strain H44/76 (B:15:P1.7,16a), was evaluated in the infant rat infection model [10].
  • We transformed H44/76 with a shuttle vector to over-express variant 1 (v.1) GNA1870 and compared the immunogenicity in mice of OMV vaccines prepared from wildtype H44/76 (v.1), the mutant, and a recombinant v.1 GNA1870 vaccine [11].

Anatomical context of H44

  • To this end, cytokine induction by isolated meningoccal LPS, wild-type N. meningitidis H44/76 (LPS+-meningococci) matched for concentrations of LPS and LPS-deficient N. meningitidis H44/76lpxA (LPS - -meningococci) was studied in human PBMCs and murine peritoneal macrophages (PMs) [12].

Associations of H44 with chemical compounds


Analytical, diagnostic and therapeutic context of H44

  • We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59 [14].
  • Here, utilizing immunohistochemistry, we have analyzed IL-18 and IL-18 receptor (IL-18R) alpha expression in the lungs of 18 patients with IPF/UIP and 13 control subjects by using monoclonal anti-IL-18 antibodies and a new monoclonal antibody for IL-18Ralpha (H44) [15].


  1. Contributions of Neisseria meningitidis LPS and non-LPS to proinflammatory cytokine response. Sprong, T., Stikkelbroeck, N., van der Ley, P., Steeghs, L., van Alphen, L., Klein, N., Netea, M.G., van der Meer, J.W., van Deuren, M. J. Leukoc. Biol. (2001) [Pubmed]
  2. Immunogenicity of outer membrane proteins in a lipopolysaccharide-deficient mutant of Neisseria meningitidis: influence of adjuvants on the immune response. Steeghs, L., Kuipers, B., Hamstra, H.J., Kersten, G., van Alphen, L., van der Ley, P. Infect. Immun. (1999) [Pubmed]
  3. Expression of foreign LpxA acyltransferases in Neisseria meningitidis results in modified lipid A with reduced toxicity and retained adjuvant activity. Steeghs, L., Berns, M., ten Hove, J., de Jong, A., Roholl, P., van Alphen, L., Tommassen, J., van der Ley, P. Cell. Microbiol. (2002) [Pubmed]
  4. Identification of a locus involved in meningococcal lipopolysaccharide biosynthesis by deletion mutagenesis. van der Ley, P., Kramer, M., Steeghs, L., Kuipers, B., Andersen, S.R., Jennings, M.P., Moxon, E.R., Poolman, J.T. Mol. Microbiol. (1996) [Pubmed]
  5. Neisseria meningitidis lipopolysaccharide modulates the specific humoral immune response to neisserial porins but has no effect on porin-induced upregulation of costimulatory ligand B7-2. Bhasin, N., Ho, Y., Wetzler, L.M. Infect. Immun. (2001) [Pubmed]
  6. Thermodynamic analysis of the interaction between a bactericidal antibody and a PorA epitope of Neisseria meningitidis. van den Elsen, J.M., van Unen, L.M., van Bloois, L., Busquets, M.A., Jiskoot, W., Hoogerhout, P., Wilting, J., Herron, J.N., Crommelin, D.J. Biochemistry (1997) [Pubmed]
  7. Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein. Van Der Ley, P., Poolman, J.T. Infect. Immun. (1992) [Pubmed]
  8. cDNAs with long CAG trinucleotide repeats from human brain. Margolis, R.L., Abraham, M.R., Gatchell, S.B., Li, S.H., Kidwai, A.S., Breschel, T.S., Stine, O.C., Callahan, C., McInnis, M.G., Ross, C.A. Hum. Genet. (1997) [Pubmed]
  9. Multiplicity of chromosome 2 histocompatibility genes: new loci, H-44 and H-45. Graff, R.J., Martin-Morgan, D., Kurtz, M.E. Immunogenetics (1987) [Pubmed]
  10. Murine monoclonal antibodies to PorA of Neisseria meningitidis show reduced protective activity in vivo against B:15:P1.7,16 subtype variants in an infant rat infection model. Toropainen, M., Saarinen, L., van der Ley, P., Kuipers, B., Käyhty, H. Microb. Pathog. (2001) [Pubmed]
  11. Improved immunogenicity of a H44/76 group B outer membrane vesicle vaccine with over-expressed genome-derived Neisserial antigen 1870. Koeberling, O., Welsch, J.A., Granoff, D.M. Vaccine (2007) [Pubmed]
  12. Neisseria meningitidis can induce pro-inflammatory cytokine production via pathways independent from CD14 and toll-like receptor 4. Sprong, T., van der Ley, P., Steeghs, L., Taw, W.J., Verver-Janssen, T.J., Netea, M.G., van der Meer, J.W., van Deuren, M. Eur. Cytokine Netw. (2002) [Pubmed]
  13. Studies of the pharmacology of a new antidepressant, S1694. Offermeier, J., Potgieter, B., Du Preez, H.G., Meiring, P.J. S. Afr. Med. J. (1977) [Pubmed]
  14. Molecular basis for a link between complement and the vascular complications of diabetes. Acosta, J., Hettinga, J., Flückiger, R., Krumrei, N., Goldfine, A., Angarita, L., Halperin, J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  15. Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis. Kitasato, Y., Hoshino, T., Okamoto, M., Kato, S., Koda, Y., Nagata, N., Kinoshita, M., Koga, H., Yoon, D.Y., Asao, H., Ohmoto, H., Koga, T., Rikimaru, T., Aizawa, H. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
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