The humoral immune system responds to antigenic challenge by
producing a diversity of antibodies specific for antigenic
determinants being presented by the foreign body, as is the case when a human becomes infected with the HIV virus. A large diversity of antibodies is produced against two primary epitopes of the HIV surface antigen, gp120, namely the V3 loop and the CD4-binding site. A better understanding of this, and other similar responses, has important implications for combating many diseases, including AIDS. However, the diversity of the immune response, coupled with the problems associated with producing human antibodies, has made it very difficult to study.
Phage display libraries provide a means of producing a large number of antibodies from a single individual, thereby facilitating the investigation of a complete immune response. These libraries have been utilised to study antibodies specific for the CD4-binding site of gp120, and, in conjunction with a binary plasmid system, the relative contributions of the heavy and light chains to specificity and function of the antibody were demonstrated.
Finally, Fab fragments specific for both metal ions and gp120 were produced, in an attempt to catalyse the peptide cleavage of gp120. This work has led to an increased understanding of antibody-antigen interactions, with specific reference to neutralising the HIV virus, and has further investigated the possibility of constructing catalytic metallo-antibodies.
Item Type:
Thesis (PhD)
Date of Award:
1993
Refereed:
No
Supervisor(s):
O'Kennedy, Richard
Uncontrolled Keywords:
Immunoglobulins; Immune response; HIV virus; AIDS; Antibodies