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PMID: 7525988 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies.

Journal of virology ·Vol. 68 ·No. 12 ·1994-12-00 ·Pages 8350-64

Moore JP, McCutchan FE, Poon SW, Mascola J, Liu J, Cao Y, Ho DD

Abstract

The reactivities of a panel of 14 monoclonal antibodies (MAbs) with monomeric gp120 derived from 67 isolates of human immunodeficiency virus type 1 of clades A through F were assessed by using an antigen-capture enzyme-linked immunosorbent assay. The MAbs used were all raised against gp120 or gp120 peptides from clade B viruses and were directed at a range of epitopes relevant to human immunodeficiency virus type 1 neutralization: the V2 and V3 loops, discontinuous epitopes overlapping the CD4-binding site, and two other discontinuous epitopes. Four of the five V3 MAbs showed modest cross-reactivity within clade B but very limited reactivity with gp120s from other clades. These reactivity patterns are consistent with the known primary sequence requirements for the binding of these MAbs. One V3 human MAb (19b), however, was much more broadly reactive than the others, binding to 19 of 29 clade B and 10 of 12 clade E gp120s. The 19b epitope is confined to the flanks of the V3 loop, and these sequences are relatively conserved in clade B and E viruses. In contrast to the limited reactivity of V3 MAbs, CD4-binding site MAbs were much more broadly reactive across clades, two of these MAbs (205-46-9 and 21h) being virtually pan-reactive across clades A through F. Another human MAb (A-32) to a discontinuous epitope was also pan-reactive. The CD4-binding site is strongly conserved between clades; but when considering the epitopes near the CD4-binding site, clade D gp120 appears to be the most closely related to clade B and clade E appears to be the least related. A tentative rank order for these epitopes is B/D-A/C-E/F. V2 MAbs reacted sporadically within and between clades, and no clear pattern was observable. While results from binding assays do not predict neutralization serotypes, they suggest that there may be antigenic subtypes related, but not identical, to the genetic subtypes.

MeSH Terms
Amino Acid Sequence Antibodies, Monoclonal Antigenic Variation Antigens, CD/metabolism Binding Sites Binding Sites, Antibody CD4 Antigens/metabolism Epitopes/analysis,chemistry HIV Antigens/genetics,immunology HIV Envelope Protein gp120/genetics,immunology HIV-1/classification,genetics,isolation & purification Humans Molecular Sequence Data
Chemicals
Antibodies, Monoclonal Antigens, CD CD4 Antigens Epitopes HIV Antigens HIV Envelope Protein gp120
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Moore J P
Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016.
McCutchan F E
Poon S W
Mascola J
Liu J
Cao Y
Ho D D
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.12.8350-8364.1994
Published
1994-12-00
Pages
8350-64
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237304
Subset
IM
Grants
NIAID NIH HHS · AI 25541 · United States
NIAID NIH HHS · N01 AI35168 · United States
External Links
PubMed source DOI: 10.1128/JVI.68.12.8350-8364.1994 PMC Full Text View journal details
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