CAREER: Biomolecular Engineering of Antigen Presentation: Development of an Interdisciplinary Research and Education Toolkit

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

The mammalian immune system demonstrates incredible power and flexibility in protection from disease and other organism processes, and the ability to stimulate controlled immune responses could revolutionize many areas of molecular medicine. Peptide antigen presentation to T cells by major histocompatibility complex proteins (MHC) is central to these immune responses; engineering MHC-peptide binding will require a detailed and quantitative understanding of the phenomena. This will require assiduous development of research tools and infrastructure for personnel training aimed at quantitative molecular design and optimization. The proposed work aims to (1) quantitatively study a related family of A related will be studied to quantitatively examine the kinetics and thermodynamics of binding between class II major histocompatibility complex protein (MHC-II) and a family of related peptide antigens; (2) elucidate correlations between peptide physicochemical properties and antigenic properties through computational structure analysis and functional studies; and (3) develop a directed evolution approach to tailoring MHC-II peptide-binding properties; (4) develop a graduate and undergraduate lecture and laboratory courses teaching state-of-art approaches in molecular biotechnology and biomolecular engineering.