| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
Innate immunity and acquired immunity play an essential role in human immune system, in which the former system recognize pathogen-associated molecular patterns and the latter non-self peptide antigens. The representative cells are macrophages and αβ T cells, respectively. Although human γδ T cells are considered to be involved in innate immunity since they recognize pyrophosphomonoesters and alkyl amines derived from pathogenic microbes, they are, on their other hand, classified as a member of acquired immunity based on their cell surface receptor generated as a result of gene rearrangement. In this study, immunological nature of human γδ T cells was elucidated by examining their recognition mechanism of nonpeptide antigens. Nitrogen-containing bisphosphonate was used in the present study. In the primary reaction, cell aggregation and interferon-γ Production were dependent on the existence of macrophage-lineage cells, indicating that antigen-presenting cells are involved in the recognition of nonpeptide antigens by γδ T cells. In addition, tumor cells were demonstrated to be able to present nonpeptide antigens to human γδ T cells in the secondary reaction. In order to elucidate the precise recognition mechanism of nonpeptide antigens by γδ T cell receptors, gene transfer system using a TCR-negative Jurkat cell line was employed, in which germline-encoded lysine residues in Jγ1.2 segment were shown to be involved in the interaction. This indicates that canonical sequence of γδ T cell receptors recognizes directly nonpeptide antigens, while γδ T cell receptors undergo gene rearrangement. Taken, together, human γδ T cells were confirmed to have two distinct characters, innate immunity and acquired immunity, on the basis of their mechanism for antigen recognition.
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