| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Sho Kyushu University . Research associate, 生体防御医学研究所, 助手 (50167649)
KIKUCHI Ikuo Kyushu University . Research associate, 生体防御医学研究所, 助手 (80169820)
KIMURA Akinori Kyushu University . Research associate, 生体防御医学研究所, 助手 (60161551)
SAKAKI Yoshiyuki Kyushu University . Professor, 遺伝情報実験施設, 教授 (10112327)
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| Research Abstract |
To investigate the genetic control of immune regulation in humans, we have already performed the population study and family study to demonstrate the existence of immune suppression genes(Is-genes), using natural antigens. In the present study, to analyse the expression of HLA-linked Is-genes in the immune response to natural antigens, such as streptococcal cell wall antigen(SCW), schistosoma japonicum antigen(Sj), cryptomeria pollen antigen(CP) and mycobacterium leprae antigen(ML) in vitro, we performed blocking experiments using various anti HLA monoclonal antibodies(mAbs). When we use SCW, Sj and ML, as challenging antigens, the proliferative response of T4 helper T cells was completely blocked by anti HLA-DR mAb. On the contrary, nonresponse, which is controlled by Is-genes through T8 suppressor T cells, was converted to high response by the addition of anti DQ mAb in the culture. Therefore, we concluded that the HLA-DR was the product of immune response gene and that the HLA-DQ it
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self was the product of Is-genes. Because Dw2 and Dw12 haplotypes were different in their phenotype of immune responsiveness to SCW or Sj, amino acid sequence of DQwl <beta> -chain of Dw12 deduced from cDNA clone established here was compared with that of DQwl <beta> of Dw2 to determine the specific epitope to induce antigen specific suppression. The hypervariable region of <beta> 1 domain was considered to be responsible for the functional difference in the immune suppression between these haplotypes. Antigen specific T8 suppressor T cells were also clearly demonstrated in CP specific IgE production system in vitro and T lymphoproliferative response to ML in vitro.
The genetic control of immune response in humans was clearly demonstrated using genetics, cellular immunology, and molecular biology. Our findings that HLA-class <II> molecules played major role in the immune response and suppression do provide a clue as to the mechanism of immune regulation and disease susceptibility in humans. Less
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