2000 Fiscal Year Final Research Report Summary
Structure and function of memory T cell marker CD26
| Project/Area Number |
11694248
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MORIMOTO Chikao The Institute of Medical Science, The University of Tokyo Professor, 医科学研究所, 教授 (30119028)
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| Co-Investigator(Kenkyū-buntansha) |
HOSONO Osamu The Institute of Medical Science, The University of Tokyo Assistant Professor, 医科学研究所, 助手 (50190210)
TANAKA Hirotoshi The Institute of Medical Science, The University of Tokyo Associate Professor, 医科学研究所, 助教授 (00171794)
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| Project Period (FY) |
1999 – 2000
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| Keywords | CD26 / M6P / IGFIIR / T cell costimulation / Dipeptidyl peptidase IV / ADA binding protein / interrnalization |
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| Research Abstract |
CD26 is a T cell activation antigen known to bind adenosine deaminase and have dipeptidyl peptidase IV activity. Cross-linking of CD26 and CD3 with immobilized mAbs can deliver a costimulatory signal that contributes to T cell activation. Our earlier studies revealed that cross-linking of CD26 induces its internalization, the phosphorylation of a number of proteins involved in the signaling pathway, and subsequent T cell proliferation. Although these findings suggest the importance of internalization in the function of CD26, CD26 has only 6 aa residues in its cytoplasmic region with no known motif for endocytosis. In the present study, we have identified the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIR) as a binding protein for CD26 and that mannose 6-phosphate (M6P) residues in the carbohydrate moiety of CD26 are critical for this binding. Activation of peripheral blood T cells results in the mannose 6 phosphorylation of CD26. In addition, the cross-linking of CD26 with an anti-CD26 antibody induces not only capping and internalization of CD26 but also colocalization of CD26 with M6P/IGFIIR.Finally, both internalization of CD26 and the T cell proliferative response induced by CD26-mediated costimulation were inhibited by the addition of M6P, but not by glucose 6-phosphate or mannose 1-phosphate. These results indicate that internalization of CD26 after cross-linking is mediated in part by M6P/IGFIIR and that the interaction between mannose 6-phosphorylated CD26 and M6P/IGFIIR may play an important role in CD26-mediated T cell costimulatory signaling.
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