Dendritic cell homologous antigenic loading initiates AIMp1-mediated TH1 immunity (IRC7P.432)
| Autor: | Matthew Halpert, Dan Liang, Vanaja Konduri, Robia Pautler, Sherry Klumpp, Ratan Bhardwaj, Jonathan Levitt, William Decker |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 194:128.13-128.13 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.194.supp.128.13 |
| Popis: | Attempts to treat cancer by vaccine immunotherapy have produced unsatisfactory results in part due to an inability to generate effective TH1 immunity. Here we demonstrate the existence of an elegant TH1 regulatory mechanism based upon release of the AIMp1 proinflammatory cytokine and elicited by the loading of dendritic cells (DC) with MHC class I and II antigenic epitopes of overlapping (homologous) amino acid sequence. Using a variety of distinct model systems, we demonstrate that DC possess a physical mechanism by which to compare amino acid sequence homology of bound class I and II epitopes, releasing AIMp1 when significant homology among such epitopes exists. AIMp1 release was shown to be upstream of microsomal CTLA-4 secretion, events that were inversely correlated and directly dependent upon the presence of homologous class I and II antigenic epitopes. Antigenic homology could mediate DC TH1 polarization and subsequent enhancement of CD8+ responses only when MHC molecules were present and able to be loaded, in an AIMp1-dependent manner, and when bound class I and II peptides shared uninterrupted sequence homology of at least five amino acid residues. Physiologic relevance and translational applicability to cancer were also demonstrated. The existence of this surprising and novel regulatory mechanism alters the paradigm by which regulation of cellular immunity is generally understood. |
| Databáze: | OpenAIRE |
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