Mapping the immune response to the outer domain of a human immunodeficiency virus-1 clade C gp120.
The outer domain (OD) of human immunodeficiency virus (HIV)-1 gp120 represents an attractive, if difficult, target for a beneficial immune response to HIV infection. Unlike the entire gp120, the OD is structurally stable and contains the surfaces that interact with both the primary and secondary cellular receptors. The primary strain-specific neutralizing target, the V3 loop, lies within the OD, as do epitopes for two cross-reactive neutralizing monoclonal antibodies (mAbs), b12 and 2G12, and the contact sites for a number of inhibitory lectins. The OD is poorly immunogenic, at least in the context of complete gp120, but purposeful OD immunization can lead to a substantial antibody response. Here, we map the antibody generated following immunization with a clade C OD. In contrast to published data for the clade B OD, the majority of the polyclonal response to the complete clade C OD is to the V3 loop; deletion of the loop substantially reduces immunogenicity. When the loop sequence was substituted for the epitope for 2F5, a well-characterized human cross-neutralizing mAb, a polyclonal response to the epitope was generated. A panel of mAbs against the clade C OD identified two mAbs that reacted with the loop and were neutralizing for clade C but not B isolates. Other mAbs recognized both linear and conformational epitopes in the OD. We conclude that, as for complete gp120, V3 immunodominance is a property of OD immunogens, that the responses can be neutralizing and that it could be exploited for the presentation of other epitopes.
Chen
Hongying
H
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Xu
Xiaodong
X
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Lin
Hsin-Hui
HH
Abnova (Taiwan) Corporation, 9th Floor, 108 Jou Tz Street, Neihu, Taipei 114, Taiwan ROC.
Chen
Ssu-Hsien
SH
Abnova (Taiwan) Corporation, 9th Floor, 108 Jou Tz Street, Neihu, Taipei 114, Taiwan ROC.
Forsman
Anna
A
Division of Infection & Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Aasa-Chapman
Marlen
M
Division of Infection & Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Jones
Ian M
IM
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D002478:Cells, Cultured; D018604:Epitope Mapping; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D016056:Immunodominant Epitopes; D010446:Peptide Fragments
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