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- W4313366173 abstract "Abstract Lymphatic endothelial cells (LECs) have been shown to archive antigen (Ag), i.e. retain Ag in its native form, for weeks after exposure. We have developed a polymeric platform that promotes targeting of Ag to lymph node (LN)-resident LECs by exploiting the sugar-binding scavenger receptors expressed by LECs, leading to longer Ag retention over 2 weeks. This targeting results in enhanced Ag archiving in LECs, even in the absence of an adjuvant or other inflammatory stimuli previously shown to be necessary for Ag archiving in LECs. 2 weeks after subcutaneous (s.c.) delivery of unmodified OVA, we observed substantial proliferation and activation of adoptively transferred OVA-specific CD8+ T cells. Immunization and subsequent Ag archiving with our targeting polymer conjugated to OVA (without adjuvant) led to reduced CD8+ T cell proliferation but higher differentiation into a central memory phenotype, both by surface receptors as well as the ratio of EOMES vs. T-bet on activated T cells. We measured MHCI-mediated presentation of OVA (SIINFEKL presented on the H-2kb molecule) on LN-LECs vs. DCs over two weeks following s.c. injection and found that Ag presentation by LECs was comparable to DCs. This demonstrates that LECs are able to cross-present archived Ag directly to CD8+ T cells, with potential implications in the prolonged maintenance of memory CD8+ T cells and design of a more effective vaccine platform." @default.
- W4313366173 created "2023-01-06" @default.
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- W4313366173 date "2019-05-01" @default.
- W4313366173 modified "2023-09-26" @default.
- W4313366173 title "Targeting antigen to lymph node lymphatic endothelial cells under steady-state to promote archiving and memory" @default.
- W4313366173 doi "https://doi.org/10.4049/jimmunol.202.supp.196.20" @default.
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