AIRRC7 - T cell selection in the thymus and implications for immune responses (P. Rodrigues)
19 بار بازدید -
2 هفته پیش
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"The molecular principles underlying T
"The molecular principles underlying T cell selection in the thymus and their implications for protective immune responses"
Pedro Rodrigues, University of Porto
Within the thymus, thymic epithelial cells (TECs) play crucial roles in T cell development. Particularly, the selection of CD4 T cells depends on interactions between TCRs expressed on T cell precursors and self-peptides:MHC II complexes presented by cortical TECs (cTECs). Yet, the molecular mechanism that controls the generation of MHC II ligands important for CD4 T cell selection remains elusive. LAMP2 is a well-recognized mediator of autolysosome maturation. We showed that LAMP2 is highly expressed in cTECs. Using thymic transplantation models into athymic mice, we showed that genetic inactivation of Lamp2 in thymic stromal cells specifically impaired the development of CD4 T cells. Mechanistically, autophagy defects in lamp2-deficient cTECs were linked to altered MHC II processing, markedly reducing CD4 TCR repertoire diversity and impairing T cell-dependent responses against Listeria monocytogenes. We have developed novel Lamp2 conditional knockout (Foxn1Cre:Lamp2floxed) mice and will present our most recent findings on the TEC-intrinsic role of Lamp2 in the establishment of T cell immunity. Our findings suggest that LAMP2 interconnects the autophagy-lysosomal axis and the processing of selecting self-peptides:MHC II complexes in cTECs, underling its implications for the generation of a broad CD4 TCR repertoire and immune responses.
AIRR Community Meeting VII – Learnings and Perspectives
June 3-6, 2024
University of Porto, Porto, Portugal
https://www.antibodysociety.org/the-a...
Pedro Rodrigues, University of Porto
Within the thymus, thymic epithelial cells (TECs) play crucial roles in T cell development. Particularly, the selection of CD4 T cells depends on interactions between TCRs expressed on T cell precursors and self-peptides:MHC II complexes presented by cortical TECs (cTECs). Yet, the molecular mechanism that controls the generation of MHC II ligands important for CD4 T cell selection remains elusive. LAMP2 is a well-recognized mediator of autolysosome maturation. We showed that LAMP2 is highly expressed in cTECs. Using thymic transplantation models into athymic mice, we showed that genetic inactivation of Lamp2 in thymic stromal cells specifically impaired the development of CD4 T cells. Mechanistically, autophagy defects in lamp2-deficient cTECs were linked to altered MHC II processing, markedly reducing CD4 TCR repertoire diversity and impairing T cell-dependent responses against Listeria monocytogenes. We have developed novel Lamp2 conditional knockout (Foxn1Cre:Lamp2floxed) mice and will present our most recent findings on the TEC-intrinsic role of Lamp2 in the establishment of T cell immunity. Our findings suggest that LAMP2 interconnects the autophagy-lysosomal axis and the processing of selecting self-peptides:MHC II complexes in cTECs, underling its implications for the generation of a broad CD4 TCR repertoire and immune responses.
AIRR Community Meeting VII – Learnings and Perspectives
June 3-6, 2024
University of Porto, Porto, Portugal
https://www.antibodysociety.org/the-a...
2 هفته پیش
در تاریخ 1403/04/12 منتشر شده
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