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214 Peptide Sequences Mimicking the C1 Region of gp120 as Potential Inducers of Antibody-Dependent Cellular Cytotoxicity (ADCC)
V. R. Gómez-Román*1, K. Ugen2, C. Cao2, K. Manoutcharian1, and G. Gevorkian1
1Inst. de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México and 2Univ. of South Florida Coll. of Med., Tampa, USA
Background: In addition to their neutralizing capacity, certain antibodies against HIV-1 can mediate the lysis of virus-infected cells by antibody-dependent cellular cytotoxicity (ADCC), a potentially favorable mechanism to be considered in the design of an HIV-1 vaccine. The objective of this study was to use a phage display peptide library to map the specificity of mAb-ID6, a murine monoclonal antibody with ADCC activity.
Methods: Filamentous phage expressing random 12-mer peptides were affinity-selected using mAb-ID6. After 3 rounds of biopanning, 39 phage clones were isolated, sequenced, and assessed for specific binding to mAb-ID6 by ELISA.
Results: 29 phage clones (74%) were able to bind specifically to mAb-ID6. Unlike the ELISA-negative phage clones, all 29 positive clones contained a -T-XX-F-XX-W-XX-D- motif in their 12-mer insert sequence, thus sharing a homology with part of the C1 region of gp120, NVTENFNMWKNNMV (a.a. 87(100). This sequence was found to be highly conserved in all known subtypes and circulating recombinant forms of HIV-1. In addition, the positive phage clones that we isolated were shown to compete with recombinant gp160 for binding to mAb-ID6, suggesting that these phages may mimic the HIV-1 epitope responsible for ID6-mediated ADCC activity.
Conclusions: The specificity of mAb-ID6 lies within a region of C1 that is highly conserved among all subtypes of HIV-1, making this epitope a suitable candidate for the induction of cross-clade ADCC. The phage clones reported here are able to mimic this epitope and could therefore be used as components of HIV-1 vaccines inducing biological activity such as ADCC.
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