| Project/Area Number |
14570286
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | TOKYO UNIVERSITY OF SCIENCE |
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Principal Investigator |
KOZONO Haruo KOZONO,Haruo, 生命科学研究所, 助教授 (80287482)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Takachika AZUMA,Takachika, 生命科学研究所, 教授 (00028234)
ODA Masayuki ODA,Masayuki, 生命科学研究所, 助手 (20318231)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | TCR / MHC / Peptide / Stability / affinity / fluctuation / agonist / antagonist / アンタゴニスト |
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| Research Abstract |
We used differential scanning calorimetry to study the thermal denaturation of murine major histocompatibility complex class II, I-Ek, accommodating hemoglobin (Hb) peptide mutants possessing a single amino acid substitution of the chemically conserved amino acids buried in the I-Ek pocket(positions 71 and 73) and exposed to the solvent (position 72).All of the I-Ek-Hb(mut) showed increased thermal stability at pH 5.5 than at pH 7.4, similar to the I-Ek-Hb(wt), which can explain the peptide exchange ftmction of MIFIC II.The thermal stability was strongly dependent on the bound peptide sequences ; the I-Ek-Hb(mut) were less stable than the I-Ek-Hb(wt), in good correlation with the relative binding affinity of each peptide to I-Ek.This supports the notion that the bound peptide is part of the completely folded MHC II molecule.The thermodynamic parameters for I-Ek-Hb(mut) folding can explain the thermodynamic origin of the stability difference, in correlation with the crystal structural analysis, and the limited contributions of the residues on the overall conformation of the I-Ek-peptide complex. We found a linear relationship between the denaturation temperature and the calorimetric enthalpy change.Thus, although the MIIC II-peptide complex could have a diverse thermal stability spectrum, depending on the amino acid sequences of the bound peptides, the conformational perturbations are limited.The variations in the MHC II-peptide complex stability would function in antigen recognition by the T cell receptor, by affecting the stability of the MIIC II-peptide-T cell receptor ternary complex.
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