2007 Fiscal Year Final Research Report Summary
Explore the cause of CDR3 shortening during thymocyte selection
| Project/Area Number |
18590178
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Tohoku University |
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Principal Investigator |
OGATA Masaki Tohoku University, Tohoku University, Graduate School of Medicine, Assistant Professor (50311907)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Tsunetoshi Tohoku University, Graduate School of Medicine, Professor (90004746)
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| Project Period (FY) |
2006 – 2007
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| Keywords | T cell receptor / Thymic selection / Thymic development / MHC / Antigen specificity / Antigen recognition |
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| Research Abstract |
T cell receptor (TCR) is composed of alpha and beta chain subunits. TCR can specifically recognize an antigen-peptide presented on antigen presenting Dells with complementarily determining region 3 (CDR3) generated after gene rearrangement. We have previously reported that the length of CDR3 shortened along with thymic T cell development. However, it remains unknown why the alteration of CDR3 length occur during T cell development. To clarify the mechanism of CDR3 shortening, we planned to analyze an alteration of CDR3 length in TCR beta chain in detail and also examine whether the change is observed in TCR alpha chain.
By using a set of congenic mice bearing different MHC haplotypes we disclosed that 1) CDR3 length in TCR beta shortened between CD4+CD8+ and either CD4+CD8- or CD4-CD8+ cells in thymus, that 2) CDR3 shortening was influenced by MHC haplotype, 3) the extent of CDR3 shortening varied considerably among Vbeta families and 4) there are similarities in the extent of CDR3 shor
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tening between homologous Vbeta subfamilies. We established an analysis method of CDR3 length in TCR alpha chain and performed the CDR3 length analysis with a large panel of primers specific for 29 Valpha families. We demonstrated in this study, for the first time, that CDR3 length shortened in both beta chain and alpha chain. In addition, we found that the extent of CDR3 shortening was heavily dependent not only on V beta chain but also Valpha chain.
It is well-known that amino acid residues on MHC alpha-helix can interact with those located at TCR V regions through crystallographic studies of TCR/peptide-MHC molecules, which are crucial to antigen recognition. We speculated that only TCR that can ensure proper configuration between MHC and V regions should be selected thorough positive and negative selections, leading to alteration of CDR3 length. We revealed an interesting fact that topology of the TCR-peptide/MHC interaction has an impact on inherent diversity of TCR in terms of CDR3 length. Less
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[Journal Article] Limited VH gene usage in B-cell clones established with nurse-like cells from patients with rheumatoid arthritis2006
Author(s)
Nakamura-Kikuoka S, Takahi K, Tsuboi H, Toyosaki-Maeda T, Maeda-Tanimura M, Wakasa C, Kikuchi N, Norioka S, Iwasaki M, Matsutani T, Itoh T, Yamane S, Takemoto H, Tsuruta Y, Shimaoka Y, Yukioka M, Suzuki R, Ochi T.
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Journal Title
Rheumatology (Oxford) 45(5)
Pages: 549-557
Description
「研究成果報告書概要(欧文)」より
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