Impact of a structural conformation of the V3 loop on the immunogenic properties of gp120 encoded in HIV -1 field isolates.
Item
-
Title
-
Impact of a structural conformation of the V3 loop on the immunogenic properties of gp120 encoded in HIV -1 field isolates.
-
Identifier
-
AAI9986349
-
identifier
-
9986349
-
Creator
-
Lee, Sang-Kyung.
-
Contributor
-
Adviser: William Boto
-
Date
-
2000
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Health Sciences, Immunology | Biology, Molecular
-
Abstract
-
The results of the study presented in this thesis show that clones of the ENV gene derived from genetically divergent HIV-1 field isolates fall into two major subsets based on the predicted secondary structure of the V3 region in gp120. One subset exemplified by the clones A-UG06c, B-RT3.12 and C-UG045 is predicted to assume a beta-turn conformation in the V3 loop, and comprises the apical tetrapeptide GPGX&barbelow;. The other subset exemplified by the clones D-UG23c and D-UG042 (apical tetrapeptide GX&barbelow;GX&barbelow;) are deficient in the expression of the beta-turn in the loop. Since secondary conformations are highly likely to confer antigenic properties in a protein backbone at least for B cells, I have used nucleic acid immunization to test the effect of the beta-turn deficiency on the immunogenic potential of rgp120 encoded in these field isolates. As hypothesized, inoculation of BALB/c mice with the ENV plasmid encoding the beta-turn-expressing rgp120 molecules resulted in the development of a vigorous antibody response to the homologous V3 loop peptides. In contrast, immunization with an rgp120 clone which is deficient in the beta-turn in the V3 loop showed no evidence of antibody development to the loop. Instead, the latter clones triggered T cell proliferative responses and markedly increased levels of IL-2 and IFN-gamma production by T cells. Significantly, reconstitution of the beta-turn conformation by site-directed mutagenesis of the V3 loop yielded rgp120 molecules which restored antibody production while diminishing the cell-mediated immune (CMI) responses to the loop. These observations demonstrate a marked impact of genetic variation on secondary conformation and immunogenic properties of gp120 encoded in divergent HIV-1 field isolates.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
