The second extracellular loop of CCR5 contains the dominant epitopes for highly potent anti-human immunodeficiency virus monoclonal antibodies.

摘要: Six mouse anti-human CCR5 monoclonal antibodies (mAbs) that showed potent antiviral activities were identified from over 26,000 hybridomas. The epitopes for these mAbs determined by using various mutants, including CCR5/CCR2B chimeras. One mAb, ROAb13, was found to bind a linear epitope in the N terminus of CCR5. Strikingly, other five derived extracellular loop 2 (ECL2). three most mAbs, ROAb12, ROAb14, and ROAb18, require residues both N-terminal (Lys171 Glu172) C-terminal (Trp190) halves ECL2 binding; two ROAb10 ROAb51, which also activities, Lys171 Glu172 but not Trp190 binding. Binding control mAb 2D7 completely relies on Glu172. Unlike 2D7, novel ROAb18 do peptide 2D7-2SK. In addition, all monkey (with Arg at position 171 instead Lys); however, does not. Since six same pool immunized mice as epitopes, we hypothesize contains dominant with activities. These multiple species detected large proportions total cell surface recognizing high binding affinity. A homology model generated aid interpretation ECL2.