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Title:Engineering Proteins Encoded by the Major Histocompatability Complex
Author(s):Brophy, Susan Eileen
Doctoral Committee Chair(s):Kranz, David M.
Department / Program:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Biochemistry
Abstract:Proteins encoded by the major histocompatability complex (MHC) were initially discovered based on their role in skin graft rejections. Years later, the physiological function of MHC proteins, as key players in the immune response to foreign pathogens, was elucidated. For instance, class I major histocompatability complex proteins (MHC) protect against foreign pathogens by binding and "presenting" antigenic peptides from bacteria, viruses or parasites. A class I MHC protein consists of a heavy chain (45 kDa) with three domains (alpha1alpha 2alpha3) and a light chain called beta2-microglobulin (12 kDa) that associates with the alpha3 domain. Peptides bind within a cleft formed by two helices of the alpha1 and alpha 2 domains. Peptide-MHC class I complexes are recognized by a receptor (T cell receptor, TCR) on cytotoxic T cells (CTL) stimulating the release of various proteins, including enzymes, that destroy the infected cells. The dynamic interactions between TCRs and peptide-MHC class I complexes have been studied extensively at the molecular level by our lab and other labs. The MHC is the most polymorphic locus known, with thousands of allelic variants. There is considerable interest in understanding the diversity of structures and peptide-binding features represented by this class of proteins. While several MHC proteins have been crystallized, many have not been amenable to structural or biochemical studies due to instability. A strategy to engineer MHC proteins is developed in the present work (Chapter two) and the approach is used to generate stabilized peptide-MHC complexes that bind to a TCR (Chapter three). Finally, factors that influence the T cell stimulatory activities of peptide-MHC class I complexes (e.g. peptide stability, peptide-MHC stability) are evaluated in Chapter four.
Issue Date:2004
Description:136 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2004.
Other Identifier(s):(MiAaPQ)AAI3130885
Date Available in IDEALS:2015-09-25
Date Deposited:2004

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