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Differential requirements for TCR down-regulation induced by anti-CD3 antibody and superantigen

Title
Differential requirements for TCR down-regulation induced by anti-CD3 antibody and superantigen
Authors
강창희
Issue Date
2003
Department/Major
대학원 분자생명과학부
Publisher
이화여자대학교 대학원
Degree
Master
Abstract
세포 표면에는 외부환경인자와 상호작용을 하기 위한 수용체가 존재한다. 수용체가 리간드라는 외부환경인자와 결합을 하게 되면 수용체가 세포 표면으로부터 세포 내부로 이동하는 과정이 일어난다. 항CD3단일클론항체와 수퍼항원은 T 림프구 수용체의 세포내 이입 과정을 유도하는 리간드들이다. 수용체의 세포내 이입 과정은 세포 신호 전달 과정을 동반하는데, 이 과정의 일부를 억제하였을 때, 항CD3단일클론항체와 수퍼항원이 세포내 이입 과정을 유도하는 데 있어서 억제되는 정도의 차별화가 이루어졌다. 그뿐만 아니라 두 리간드가 세포내 이입과정을 유도할 때, T 림프구 수용체의 일부를 이루는 단백질의 분해 양상도 달랐다. 이로써 두 리간드가 T 림프구 세포내 이입 과정을 조절하는 데 있어서 서로 다른 세포 신호 전달 과정을 필요로 할 것이라고 생각되었고, 이 같은 생각은 T 림프구 수용체를 구성하는 단백질의 최종 분해 여부의 차별화로 뒷받침 될 수 있다. ; TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. It is known that two distinct pathways exist for down-regulation of the TCR. One pathway is activated following TCR ligation and is dependent on tyrosine phosphorylation. The other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3γ di-leucine-based receptor-sorting motif. Although TCR down-regulation induced by anti-CD3 antibody or superantigen has been known to ligand-induced down-regulation distinct from PKC-induced down-regulation, the present study shows that the two ligands have differential requirements for TCR down-regulation. Anti-CD3 antibody-induced TCR down-regulation was dependent on PTK activation and tyrosine phosphorylation. Superantigen-induced TCR down-regulation was inhibited by latrunculin B implying that actin cytoskeleton was involved in the down-regulation. Furthermore, when TCR down-regulation induced by each ligand was subjected to conditions that selectively inhibit clathrin-mediated endocytosis, TCR down-regulation stimulated by anti-CD3 antibody was severely impaired. In contrast, superantigen-induced TCR down-regulation was only slightly inhibited. These results indicate that clathrin-mediated endocytosis is the predominant pathway for anti-CD3 antibody-induced TCR down-regulation. Consistent with this idea, the fate of TCR was also different when stimulated with each ligand. The degradation of CD3ζ was induced only by anti-CD3 antibody. These results are discussed with respect to the differential requirements for TCR down-regulation and in consequence the use of different endocytic machineries in response to the two stimuli.
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