Persistent Link:
http://hdl.handle.net/10150/187475
Title:
The molecular origins of the recombining immune system.
Author:
Bernstein, Ralph Michael.
Issue Date:
1996
Publisher:
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:
This dissertation examines the molecular origins of the recombining immune system. Two strategies were adopted involving the examination of the immune system of the most ancient extant organism possessing the vertebrate type immune response, the Carcharhine shark. First, the structural components of a primordial immunoglobulin (Ig) were examined on a molecular level. This revealed a new class of Ig termed IgW. Although IgW is the largest Ig yet described, with 7 bona fide Ig domains, it maintains the canonical residues typified by heavy chain V and C-regions. Because of these canonical residues, IgW is thought to both dimerise with light chains and associate with antigen as a typical heavy chain. IgW also possesses V-regions which are more similar to its own C-regions than any Ig yet described. In phylogenetic tree analysis, the IgW molecule is continually found to be the "root" of the Ig V and C-region trees constructed from the known V and C-region genes. This, and IgW's V and C-region similarities support the contention that IgW is the most ancient Ig yet cloned, possibly being most closely related to the primordiallg gene. The second strategy adopted was the examination of the shark's V(O)J rearrangement machinery. The recombinase activating gene I (RAG I) is responsible for creating diversity in all extant gnathastomes, which is the hallmark of the recombining immune system. The shark RAG I was found to be extremely homologous to the known vertebrate RAG I genes, both at the nucleotide and amino acid levels (∼64 % identical at both levels). Homology domains identified by the comparison of the vertebrate RAG I's and the shark RAG I prompted sequence comparison analyses which suggested similarity of the RAG I and II genes to the integrase family and the integration host factor genes, respectively, of the bacterial site specific recombination system. This was used in conjunction with several shark VH "hairpin" detecting rearrangement intermediate experiments to propose a new and more complete model of V(D)J recombination.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Microbiology and Immunology; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Marchalonis, John J.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe molecular origins of the recombining immune system.en_US
dc.creatorBernstein, Ralph Michael.en_US
dc.contributor.authorBernstein, Ralph Michael.en_US
dc.date.issued1996en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © 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.en_US
dc.description.abstractThis dissertation examines the molecular origins of the recombining immune system. Two strategies were adopted involving the examination of the immune system of the most ancient extant organism possessing the vertebrate type immune response, the Carcharhine shark. First, the structural components of a primordial immunoglobulin (Ig) were examined on a molecular level. This revealed a new class of Ig termed IgW. Although IgW is the largest Ig yet described, with 7 bona fide Ig domains, it maintains the canonical residues typified by heavy chain V and C-regions. Because of these canonical residues, IgW is thought to both dimerise with light chains and associate with antigen as a typical heavy chain. IgW also possesses V-regions which are more similar to its own C-regions than any Ig yet described. In phylogenetic tree analysis, the IgW molecule is continually found to be the "root" of the Ig V and C-region trees constructed from the known V and C-region genes. This, and IgW's V and C-region similarities support the contention that IgW is the most ancient Ig yet cloned, possibly being most closely related to the primordiallg gene. The second strategy adopted was the examination of the shark's V(O)J rearrangement machinery. The recombinase activating gene I (RAG I) is responsible for creating diversity in all extant gnathastomes, which is the hallmark of the recombining immune system. The shark RAG I was found to be extremely homologous to the known vertebrate RAG I genes, both at the nucleotide and amino acid levels (∼64 % identical at both levels). Homology domains identified by the comparison of the vertebrate RAG I's and the shark RAG I prompted sequence comparison analyses which suggested similarity of the RAG I and II genes to the integrase family and the integration host factor genes, respectively, of the bacterial site specific recombination system. This was used in conjunction with several shark VH "hairpin" detecting rearrangement intermediate experiments to propose a new and more complete model of V(D)J recombination.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairMarchalonis, John J.en_US
dc.contributor.committeememberHersh, Evan M.en_US
dc.contributor.committeememberBernstein, Harrisen_US
dc.contributor.committeememberCress, Anneen_US
dc.contributor.committeememberSchluter, Samuel F.en_US
dc.identifier.proquest9626501en_US
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