HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hager-Braun, C. Articles by Tomer, K. B. Search for Related Content PubMed PubMed Citation Articles by Hager-Braun, C. Articles by Tomer, K. B.

The HIV-Neutralizing Monoclonal Antibody 4E10 Recognizes N-Terminal Sequences on the Native Antigen¹

Christine Hager-Braun^2,*, Hermann Katinger and Kenneth B. Tomer^*

^* National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709; and University for Natural Resources and Applied Life Sciences, Institute of Applied Microbiology, Vienna, Austria

Characterization of the epitope recognized by the broadly neutralizing anti-HIV Ab 4E10 has, heretofore, focused on a linear sequence from the gp41 pretransmembrane region (PTMR). Attempts to generate neutralizing Abs based on this linear epitope sequence have been unsuccessful. We have characterized the antigenic determinants on recombinant glycosylated full-length Ags, and nonglycosylated and truncated Ags recognized by 4E10 using epitope extraction and excision assays in conjunction with MALDI mass spectrometry. The mAb recognized the peptides ³⁴LWVTVYYGVPVWK⁴⁶ and ⁵¹²AVGIGAVFLGFLGAAGSTMGAASMTLTVQAR⁵⁴² located at the N-terminal region of gp120 and gp41, respectively. Immunoassays verified AV(L/M)FLGFLGAA as the gp41 epitope core. Recognition of the peptide from the gp41 PTMR was detected only in constructs in which the N termini of the mature envelope proteins were missing. In this region, the epitope core is located in the sequence ⁶⁷²WFDITNWLWY⁶⁸¹. We hypothesize that the hydrophobic surface of the paratope functions as a "trap" for the viral sequences, which are responsible for insertion into the host cell membrane. As the N-terminal region of gp120, the fusogenic peptide of gp41, and the PTMR of gp41 show high sequence homology among various HIV strains, this model is consistent with the broadly neutralizing capabilities of 4E10.

This article has been cited by other articles:

				L. G. Perez, M. R. Costa, C. A. Todd, B. F. Haynes, and D. C. Montefiori Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: a Specific Role for Antibodies against the Membrane-Proximal External Region of gp41 J. Virol., August 1, 2009; 83(15): 7397 - 7410. [Abstract] [Full Text] [PDF]

				M. Montero, N. E. van Houten, X. Wang, and J. K. Scott The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design Microbiol. Mol. Biol. Rev., March 1, 2008; 72(1): 54 - 84. [Abstract] [Full Text] [PDF]