Effects of HCDR transplantation on the biochemical properties of diverse antibody active sites

The diverse active site structures of Map 4-4-20 (pocket; anti-fluorescein) and 04-01(cleft; anti-ssDNA) have been studied extensively (Herron et al., 1989; Denzin et al., 1991; Herron et al., 1991; Denzin et al., 1993; Rumbley et al., 1993), and have led to the hypothesis that the unique biochemical properties exhibited by the active sites of these two antibodies are a function of properties intrinsic to their respective heavy chains, as the light chains are nearly identical, while the heavy chains differ significantly (Bedzyk et al., 1990; Smith et al., 1989; Smith and Voss, 1990). In order to investigate this hypothesis, hybrid single chain antibodies were generated by transplanting heavy chain framework and complementarity determining regions (HFRs and HCDRs) from anti-fluorescein SCA 4-4-20 into the H-chain of anti-ssDNA 04-01 as a means to identify those HFRs and HCDRs required to convey the biochemical properties (structure, function, and stability) of diverse antibody active sites, i.e., a cleft versus a pocket. Such analyses yielded significant information concerning the dependence of antibody active site properties on heavy chain primary structure, which could be applied to other systems to aid in the understanding of the relationships between primary structure and the various biochemical properties exhibited by a protein.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Gulliver, Gene Allen

Contributors dc:contributor

• Voss, Edward W., Jr.

• Biology, Microbiology
• Health Sciences, Immunology

Statement dc:rights

• Copyright 1995 Gulliver, Gene Allen

Language dc:language

eng

Identifier

AAI9543599
(UMI)AAI9543599

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/19828