REGULATION AND FUNCTION OF MARCH1: MODULATION OF IMMUNITY THROUGH UBIQUITINATION
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azu_etd_11274_sip1_m.pdf
Author
Jabbour, Maurice E.Issue Date
2010Advisor
Lybarger, Lonnie P.Committee Chair
Lybarger, Lonnie P.
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The University of Arizona.Rights
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.Abstract
The activation of the immune system, particularly adaptive immunity, in response to a pathogen ( e.g. viruses) relies on complex network of cell interactions including those between lymphocytes (T cells) and dendritic cells (DC). In its simplest form, the DC-mediated activation of T cells is dependent on 1) binding of antigen presenting molecules (MHC class I and class II) and their peptides to the T cell receptor and 2) interaction between costimulatory molecules (CD80 and CD86) on DC and their receptors on T cells. Together these signaling events induce an optimal T cell-dependent immune response. Viruses, including herpesviruses and poxviruses, using evolutionarily conserved ubiquitin E3 ligases, appropriate cellular ubiquitin pathways for targeting immune molecules (CD86 or MHC), thereby evading the immune response. The notion that two evolutionarily divergent virus families share conserved ubiquitin E3 ligases suggested that viruses have acquired these enzymes from the host. Indeed, a set of cellular ubiquitin E3 ligases, termed membrane-associated RING-CH proteins (MARCH), was identified in mammalian genomes. Unlike their viral orthologs, cellular E3 ligases including MARCH proteins have regulatory functions in various cellular processes and, therefore, must be tightly controlled to prevent inadvertent effects to the host. Interestingly, due to its lymphoid-restricted expression and targeting of CD86 and MHC class II levels, MARCH1 is potentially critical for the function of DC. Furthermore, since DC are essential players in the regulation of the immune response (as evident by immune deficiencies observed following ablation of DC), MARCH1 should play a critical role in immunity. Therefore, the work presented in this thesis explores the regulation and function of MARCH1 in DC.Type
textElectronic Dissertation
Degree Name
Ph.D.Degree Level
doctoralDegree Program
ImmunobiologyGraduate College