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Abstract: 6189

A27 - HIV-specific humoral immunity 15 A27


A novel epitope model presented by 7mer constrained peptide indicates the minimal gp41
sequence required for highly specific recognition by broadly neutralizing anti-HIV-1 mAb 2F5

Y. Palacios-Rodriguez1, T. Gazarian2, K. Gazarian3


1Institute
of Biomedical Research, Mexican National Autonomous University, Genomic Medicine and Environmental
Toxicology, D.F., Mexico, 2Mexican National Autonomous University, D.F., Mexico, 3Institute of Biomedical Research, Mexican
National Autonomous University, Molecular Biology and Biotechnology, D.F., Mexico

Background: The monoclonal antibody 2F5 (mAb 2F5) is one of the three broadly neutralizing human antibodies identified to
date that recognizes the HIV-1 gp41 MPER (membrane proximal exterior region). Evidence so far indicates that the gp41
ELDKWA or a longer sequence of gp41 form the 2F5 epitope. In previous reports the screening with 2F5 of m13 gpVIII-fusion
peptide libraries 2F5 recognized DKW as minimal epitope, consistent with its binding and neutralization functions but not for
eliciting neutralizing antibody.
Methods: Using the mAb 2F5, we screened a 12mer linear and a 7mer constrained gpIII-fusion phage-displayed peptide
libraries (BioLabs Inc., USA), each containing 2.7E9 different sequences. Samples from the first, second and third biopanning
rounds were plated, individual plaques amplified and sequences of peptides were deduced from DNA sequences.
Results: When 2F5 screened for structures resembling its natural epitope in a 12mer linear library, it retrieved peptides with
variations as DKW, DRW, DRWA and LDRWA, as in previous reports. However in constrained 7mer library, all the 53 selected
clones (45 different) contained exclusively C-DKWAxx-C or C-xxLDKWA-C sequences (“x” denoting a variable position),
rejecting every amino acid variation. The data imply that the 7mer constrained peptide forming a loop contains an adequate
structural context for the natural epitope core-like conformation (most probably type-1 beta-turn).
Conclusions: According to this model, the minimal requirement for the highly specific epitope recognition by mAb 2F5 is the
presence of the conserved gp41 DKWA sequence in the structural context of 7mer potentially cyclic peptide and the presence
of the leucine in LDKWA improves the binding further.

TOP300_A
Country(ies) of Research: Mexico
Presenter: Ms. PhD Yadira Palacios-Rodriguez, Institute of Biomedical Research, Mexican National Autonomous
University, D.F. [Mexico]
Prizes/Awards: Women's Prize, ANRS/IAS prize, IAS Young Investigator Award