Project/Area Number |
11670325
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
FUKUI Yoshinori Medical Institute of Bioregulation, KYUSHU UNIVERSITY Associate Professor, 生体防御医学研究所, 助教授 (60243961)
|
Co-Investigator(Kenkyū-buntansha) |
SHIRASAWA Senji Medical Institute of Bioregulation, KYUSHU UNIVERSITY Research Associate, 生体防御医学研究所, 助手 (10253535)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
|
Keywords | T cell differentiation / CD4^+CD8^+ thymocytes / TCR / MHC / self peptides / positive selection / Thy1 molecule / 単クローン抗体 / TCR-MHC / ペプチド複合体相互作用 / アポトーシス / Thy-1 |
Research Abstract |
Although the diversity of αβ T cell receptors (TCRs) theoretically reaches 10^<15> by random rearrangement of five gene segments and random nucleotide addition, mature T cells express highly selected TCRs in that they exhibit tolerance to self-antigenic peptides and restriction by self-MHC molecules. This mainly results from two reciprocal selection processes, positive and negative selection, acting at CD4^+CD8^+ stage during T cell development in the thymus. With the use of the mAb specific for CD4^+CD8^+ thymocytes, we found that CD4^+CD8^+ thymocytes lacking TCR- MHC/peptide complex interaction specifically express multimerized Thy1 molecules. On the other hand, we developed several transgenic-knockout mouse lines expressing distinct peptides as a single species. By comparing T cell differentiation among these mice, we found positive selection is both specific and degenerate, dependending on the amino acid residues at TCR contacts of the selecting self-peptides.
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