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PIK3IP1/TrIP - Regulation of T Cell Activation and Mechanisms of Expression
PIK3IP1/TrIP - Regulation of T Cell Activation and Mechanisms of Expression
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103001
- ISBN
- 9798315794660
- DDC
- 616.079
- 서명/저자
- PIK3IP1/TrIP - Regulation of T Cell Activation and Mechanisms of Expression
- 발행사항
- [Sl] : University of Pittsburgh, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 125 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Kane, Lawrence.
- 학위논문주기
- Thesis (Ph.D.)--University of Pittsburgh, 2025.
- 초록/해제
- 요약The protein known as PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation. However, it is unclear how this downregulation is controlled. Using a novel monoclonal antibody that robustly stains cell-surface TrIP, we demonstrate that TrIP is lost from the surface of activated T cells in a manner dependent on the strength of signaling through the T cell receptor and specific downstream signaling pathways, in particular classical PKC isoforms. TrIP expression returns by 24 h after stimulation, suggesting that it may play a role in resetting T cell receptor signaling at later time points. Our data shows that the loss of TrIP from the surface is mediated via PKC-activity leading to ADAM10/17 release and subsequent TrIP cleavage. We provide data detailing how upon TCR activation, we find an increased inflammatory CD8 transcriptional profile in the absence of TrIP regulation. Furthermore, we show that this inflammatory activity leads to increased anti-tumor immunity in murine tumor models. Finally, we present evidence that TrIP regulation may serve to regulate T cell clonal responses in disease models, in that its absence we observe lower frequencies of dominant antigen clones.
- 일반주제명
- Immunology
- 일반주제명
- Cellular biology
- 일반주제명
- Genetics
- 키워드
- Immunotherapy
- 키워드
- T cell
- 키워드
- Phosphorylation
- 기타저자
- University of Pittsburgh Microbiology and Immunology
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798315794660
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aMurter, Benjamin Matthew.▼0(orcid)0000-0003-3035-3782
■24510▼aPIK3IP1/TrIP - Regulation of T Cell Activation and Mechanisms of Expression
■260 ▼a[Sl]▼bUniversity of Pittsburgh▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a125 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Kane, Lawrence.
■5021 ▼aThesis (Ph.D.)--University of Pittsburgh, 2025.
■520 ▼aThe protein known as PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation. However, it is unclear how this downregulation is controlled. Using a novel monoclonal antibody that robustly stains cell-surface TrIP, we demonstrate that TrIP is lost from the surface of activated T cells in a manner dependent on the strength of signaling through the T cell receptor and specific downstream signaling pathways, in particular classical PKC isoforms. TrIP expression returns by 24 h after stimulation, suggesting that it may play a role in resetting T cell receptor signaling at later time points. Our data shows that the loss of TrIP from the surface is mediated via PKC-activity leading to ADAM10/17 release and subsequent TrIP cleavage. We provide data detailing how upon TCR activation, we find an increased inflammatory CD8 transcriptional profile in the absence of TrIP regulation. Furthermore, we show that this inflammatory activity leads to increased anti-tumor immunity in murine tumor models. Finally, we present evidence that TrIP regulation may serve to regulate T cell clonal responses in disease models, in that its absence we observe lower frequencies of dominant antigen clones.
■590 ▼aSchool code: 0178.
■650 4▼aImmunology
■650 4▼aCellular biology
■650 4▼aGenetics
■653 ▼aImmunotherapy
■653 ▼aT cell
■653 ▼aMonoclonal antibody
■653 ▼aAnti-tumor immunity
■653 ▼aPhosphorylation
■690 ▼a0982
■690 ▼a0379
■690 ▼a0369
■71020▼aUniversity of Pittsburgh▼bMicrobiology and Immunology.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0178
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356604▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
