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Principal Investigator: Beth Ann Tamburini
Organization: UNIVERSITY OF COLORADO DENVER
Fiscal Year: 2024
Award: $459,647
Funding agency: National Institute of Allergy and Infectious Diseases
Project summary:
We and others have demonstrated that antigens derived from infectious viral infections persist in the host for
extended periods of time, well beyond the time in which the infection is cleared from the host. Our lab has
specifically identified that antigens derived from both vaccination and viral infections persist or are archived by
the host lymphatic endothelial cells (LEC)s, identifying the source of archived antigens. We have published
that this archived antigen maintains a more effector like pool of antigen specific memory cells which enhances
the clearance of a secondary infectious challenge. Identification of key mechanisms involved in antigen
archiving during vaccination is critical for our understanding of enhanced protective immunity to vaccination.
While we have established many important criteria for antigen archiving and protective immunity, in this
renewal application we aim to dive deeper into the cell types involved and the processes required. We aim to
better appreciate how the expression of subset specific genes, now discovered in both lymphatic endothelial
cells and dendritic cells, may be required for antigen handling, the implications of which could affect antigen
archiving and protective immunity. We have established a novel methodology leveraging the 10x genomics
platform to identify DNA-antigen conjugates for the study of antigen dispersal over long periods of time. With
this methodology and technology in hand we now have the capability to accurately and faithfully measure cell
types that acquire antigens as well as the exact number of antigens within each cell over time. Using these
studies we have identified several novel findings based on antigen amount and transcriptional signature to lead
us to the hypothesis that specific LECs and DCs, based on their transcriptional program, contribute to the
acquisition, retention and exchange of antigens. Furthermore, this handling of antigens by LECs and DCs can
be manipulated by other inflammatory events that cause antigen release and presentation, and as a result,
improve immune responses to secondary and heterologous infections.
Terms: <Address><Affect><Antigen Presentation><Antigens><Archives><Attenuated Vaccines><Award><BB2><Bar Codes><Body Tissues><CD54><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><Caveolin Proteins><Caveolins><Cell Body><Cell Communication><Cell Communication and Signaling><Cell Function><Cell Interaction><Cell Mediated Immunology><Cell Physiology><Cell Process><Cell Shape><Cell Signaling><Cell-Mediated Immunity><Cell-to-Cell Interaction><Cells><Cellular Function><Cellular Immunity><Cellular Physiology><Cellular Process><Communication><Conjugate Vaccines><DNA><Data><Dendritic Cells><Deoxyribonucleic Acid><Development><Event><Exocytosis><Expression Signature><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Funding><Future><Gene Expression Profile><Gene Transcription><Genes><Genetic Transcription><Grips><Hand><Hematopoietic><ICAM-1 Gene><ICAM1><ICAM1 gene><Immune memory><Immune response><Immunity><Immunologic Memory><Immunological Memory><Immunological response><Infection><Inflammation><Inflammatory><Intracellular Communication and Signaling><Lead><Learning><Live-attenuated Vaccine><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic><Lymphatic Endothelial Cells><Lymphatic nodes><Measures><Memory><Messenger RNA><Metabolic Protein Degradation><Methodology><Methods><Molecular><Pb element><Process><Proliferating><Protein Turnover><Proteins><Publishing><RNA Expression><Regulatory Protein Degradation><SCmRNAseq><Secondary to><Signal Transduction><Signal Transduction Systems><Signaling><Single cell mRNA seq><Source><Subcellular Process><Surface><T cell response><T memory cell><T8 Cells><T8 Lymphocytes><Techniques><Technology><Time><Tissues><Transcription><Vaccination><Vaccine Design><Vaccines><Veiled Cells><Viral><Viral Antigens><Viral Diseases><Virus><Virus Diseases><adaptive immune response><anamnestic reaction><antigen based detection><antigen detection><barcode><biological signal transduction><cell type><design><designing><detect antigen><developmental><emerging pathogen><flow cytophotometry><gene expression pattern><gene expression signature><genomic platform><global gene expression><global transcription profile><grasp><hands><heavy metal Pb><heavy metal lead><hemopoietic><host response><immune system response><immunization strategy><immunogen><immunoresponse><improved><live vaccine><live vaccines><lymph gland><lymph nodes><lymphnodes><mRNA><memory T lymphocyte><new pathogen><novel><novel pathogen><prevent><preventing><programs><protein degradation><secondary immune response><secondary infection><single cell mRNA sequencing><subcutaneous><subdermal><trafficking><transcriptional profile><transcriptional signature><transcriptome><vaccination strategy><vaccine strategy><viral infection><virus antigen><virus infection><virus-induced disease>