ANTIGEN-EXPERIENCED DENDRITIC CELLS
Isolate Antigen-Experienced DC Directly Ex Vivo. Using an antibody that detects peptide-MHC II (pMHCII) complexes specific for HEL protein in the context of I-Ak, we can isolate multiple cellular subsets of pMHCII+ DC in the LN draining the site of antigen administration. We will extend these studies across into different priming regime and into the boost phase of immune memory at the time of antigen recall in vivo
Evaluate the Impact of Adjuvant on DC Maturation and Function. Our initial studies identify multiple pMHCII+ DC subsets that emerge synchronously with separable gene expression programs using one type of adjuvant. Varying the adjuvant varies the cellular presentation and molecular context of pMHCII. Hence, we will examine how these changes in maturation impact DC function in vivo.
Define How pMHCII+ DC Controls Adaptive Immunity. Our immunization protocols emphasize Th cell regulated B cell immunity. We will examine how the changes in pMHCII+ DC can alter clonal selection and subsequent effector cell function in the Th cell compartment. How these changes then cascade throughout the B cell response to antigen and the establishment of high affinity B cell memory.
| These studies will enhance our understanding of adjuvants and how they control the innate and adaptive immune system. We will examine the mechanism of adjuvanticity at the cellular and molecular levels to define and can then refine adjuvant mode of action in vivo. Over the course of these studies, we will provide new means to more rationally evaluate protein sub-unit vaccination. These studies may also identify useful molecular targets for novel adjuvants and immunotherapeutics with general application in the management of infectious disease. |
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| RESEARCH AREA |
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1. Antigen-experienced Dendritic Cells more |
| 2. Antigen-specific Helper T Cell Immunity more |
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| 4. Antigen-specific B Cell Immunity more |
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