Structural analysis of the human immunodeficiency virus-binding domain of CD4. Epitope mapping with site-directed mutants and anti-idiotypes

doi:10.1084/jem.170.4.1319

This Article

	Full Text (PDF, 1122K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Sattentau, Q. J.
	Articles by Truneh, A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Sattentau, Q. J.
	Articles by Truneh, A.


Social Bookmarking

	What's this?

ARTICLES

Structural analysis of the human immunodeficiency virus-binding domain of CD4. Epitope mapping with site-directed mutants and anti-idiotypes

QJ Sattentau, J Arthos, K Deen, N Hanna, D Healey, PC Beverley, R Sweet and A Truneh
Academic Department of Genito Urinary Medicine, University College and Middlesex School of Medicine (UCMSM), London, UK.

The CD4 molecule, a differentiation marker expressed primarily by T lymphocytes, plays an important role in lymphocyte activation. CD4 is also the receptor for HIV. A number of recent studies have localized the high affinity binding site of the HIV envelope glycoprotein, gp120, to the NH2-terminal (V1) domain of CD4, a region with sequence and predicted structural homology with Ig kappa chain V domains (V kappa). In this report, we show that V1 bears structural similarities with V kappa regions through detailed epitope mapping of 26 CD4 mAbs. The binding sites of these mAbs were initially defined relative to one another by crossblocking analysis and were then localized to specific domains of CD4 in blocking studies with truncated, soluble CD4 proteins. The epitopes within the V1 domain were mapped in detail with a panel of 17 substitution mutants, and the specificities of several mAbs that appear to recognize very similar epitopes were examined in crossblocking studies with anti-idiotype antibodies. The location of the epitopes is consistent with a V kappa-like structure of V1. Most of the epitopes lie within regions of predicted exposed loops. A number of these epitopes span discontinuous residues in the linear sequence that lies in close proximity in an Ig fold. Alignment of CD4 V1 with the Ig V kappa chains places these epitopes within stretches corresponding to the complimentarity-determining regions. This epitope analysis is relevant for a vaccine strategy for HIV based on anti-idiotype antibodies to CD4 mAbs and for studies with CD4 antibodies on the role of CD4 in T lymphocyte activation.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Perdomo, M. F., Levi, M., Sallberg, M., Vahlne, A. (2008). From the Cover: Neutralization of HIV-1 by redirection of natural antibodies. Proc. Natl. Acad. Sci. USA 105: 12515-12520 [Abstract] [Full Text]
Bes, C., Briant-Longuet, L., Cerutti, M., Heitz, F., Troadec, S., Pugniere, M., Roquet, F., Molina, F., Casset, F., Bresson, D., Peraldi-Roux, S., Devauchelle, G., Devaux, C., Granier, C., Chardes, T. (2003). Mapping the Paratope of Anti-CD4 Recombinant Fab 13B8.2 by Combining Parallel Peptide Synthesis and Site-directed Mutagenesis. J. Biol. Chem. 278: 14265-14273 [Abstract] [Full Text]
Fouts, T., Godfrey, K., Bobb, K., Montefiori, D., Hanson, C. V., Kalyanaraman, V. S., DeVico, A., Pal, R. (2002). Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques. Proc. Natl. Acad. Sci. USA 99: 11842-11847 [Abstract] [Full Text]
Guillon, C., Schutten, M., Boers, P. H. M., Gruters, R. A., Osterhaus, A. D. M. E. (2002). Antibody-Mediated Enhancement of Human Immunodeficiency Virus Type 1 Infectivity Is Determined by the Structure of gp120 and Depends on Modulation of the gp120-CCR5 Interaction. J. Virol. 76: 2827-2834 [Abstract] [Full Text]
Ferrer, M., Harrison, S. C. (1999). Peptide Ligands to Human Immunodeficiency Virus Type 1�gp120 Identified from Phage Display Libraries. J. Virol. 73: 5795-5802 [Abstract] [Full Text]
Andersson, H., Kappeler, F., Hauri, H.-P. (1999). Protein Targeting to Endoplasmic Reticulum by Dilysine Signals Involves Direct Retention in Addition to Retrieval. J. Biol. Chem. 274: 15080-15084 [Abstract] [Full Text]
Mondor, I., Ugolini, S., Sattentau, Q. J. (1998). Human Immunodeficiency Virus Type 1�Attachment to HeLa CD4 Cells Is CD4 Independent and gp120 Dependent and Requires Cell Surface Heparans. J. Virol. 72: 3623-3634 [Abstract] [Full Text]
Briant, L., Robert-Hebmann, V., Sivan, V., Brunet, A., Pouyssegur, J., Devaux, C. (1998). Involvement of Extracellular Signal-Regulated Kinase Module in HIV-Mediated CD4 Signals Controlling Activation of Nuclear Factor-{kappa}B and AP-1 Transcription Factors. J. Immunol. 160: 1875-1885 [Abstract] [Full Text]
Harrison, S.C., Wang, J., Yan, Y., Garrett, T., Liu, J., Moebius, U., Reinherz, E. (1992). Structure and Interactions of CD4. Cold Spring Harb Symp Quant Biol 57: 541-548 [Abstract]
Lenert, P, Kroon, D, Spiegelberg, H, Golub, E., Zanetti, M (1990). Human CD4 binds immunoglobulins. Science 248: 1639-1643 [Abstract]