Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
Molecular characterization of a panel of HIV-1 broadly neutralizing, CD4 binding site directed human anti-gp120 monoclonal antibodies (MAbs).
Int Conf AIDS. 1992 Jul 19-24;8(1):Mo13 (abstract no. MoA 0046). Unique Identifier : AIDSLINE ICA8/92400002 Marasco WA; Bagley J; Posner M; Dillon P; Rosen C; Robinson J; Haseltine WA; Sodroski J; New England Deaconess Hospital, Boston, MA.
Abstract:
Two classes of neutralizing antibodies (Abs) are elicited against HIV-1 in infected humans: type-restricted and broadly reactive. The best characterized of the type-restricted Abs are those directed against the V3 loop. Envelope glycoprotein variation within the V3 loop and outside the loop can allow for escape of viruses from neutralization of these Abs. Later in the course of HIV-1 infection in humans, Abs capable of neutralizing a wider range of HIV-1 isolates appear. A subset of the broadly reactive Abs, found in most HIV-1 infected humans, interferes with the binding of gp120 and CD4. These Abs appear to be reactive with a discontinuous epitope on gp120 which encompasses the CD4 binding region. To understand the molecular nature of the broadly neutralizing Abs which are directed at or near the CD4 binding domain of gp120, we have cloned the rearranged heavy and light chains of three well characterized, broadly neutralizing human anti-gp120 Mabs F105, 15e and 2IH. We will present a detailed molecular analysis of VDJ (heavy chain) and VJ (light chain) gene rearrangement for these MAbs. The germline V region genes from which both the rearranged heavy and light chains are derived have been identified. By comparison of the rearranged F105, 15e and 2IH heavy and light chain genes with their germline genes, we can identify the somatic mutations which have arisen in both the framework and CDR regions of these V region genes as well as the similarities and differences among these MAbs. We will also present a comparative molecular analysis of these MAbs with other non-CD4 binding site human anti-gp120 MAbs. These studies provide the molecular basis for investigating the humoral immune response to the CD4 binding domain of gp120, for determining if the human immune response is restricted in its use of heavy and light chain germline V region genes and for providing a framework for the development of immunotherapeutic human MAbs.
Keywords: Antibody Specificity Antigenic Variation Antigens, CD4/*METABOLISM Binding Sites Epitopes/*IMMUNOLOGY/METABOLISM Gene Rearrangement, B-Lymphocyte, Heavy Chain Gene Rearrangement, B-Lymphocyte, Light Chain Human HIV Antibodies/CLASSIFICATION/GENETICS/*IMMUNOLOGY/METABOLISM HIV Envelope Protein gp120/*IMMUNOLOGY/METABOLISM HIV-1/*IMMUNOLOGY Neutralization Tests Peptide Fragments/*IMMUNOLOGY ABSTRACT 921230
M92C5345
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
