From: Natural anti-CCR5 antibodies in HIV-infection and -exposure
Table 1. Biological properties of some monoclonal and natural antibodies to CCR5; modified from [36]. | |||||
---|---|---|---|---|---|
Antibody | Source | Binding domain | Epitope(s) | Biologic properties | References |
2D7 | mAb | ECL2 | Q170, K171, E172, W190 | Inhibition of chemokine binding Inhibition of cell activation (no Ca++ flux) R5-HIV blocking | [27] |
PA9 | mAb | N-term ECL2 | D2, Y3, Q4, S7, P8, N13 Y176, T177 | Inhibition of chemokine binding | [27] |
PA14 PRO140 | mAb hu mAb | N-term ECL2 | D2 R168, Y176 | Inhibition of chemokine binding Inhibition of cell activation (no Ca++ flux) R5-HIV blocking | [27] |
HGS004 (HGS101) | hu mAb | ECL2 | Not available | Inhibition of chemokine binding without signaling HIV blocking | [57] |
MC-1 | mAb | ECL2 | Not available | Inhibition of CCL4/MIP-1beta and CCL5/RANTES binding CCR5 dimerization CCR5 internalization Inhibition of R5-HIV binding | [26] |
MC-4 | mAb | ECL2 | Not available | CCL5/RANTES-mediated signaling Inhibition of CCR5 endocytosis | [26] |
MC-6 | mAb | Multi-domain | conformational, multi-domain epitope including K171, E172 | CCL5/RANTES signaling without CCR5 internalization | [26] |
RoAb12 RoAb14 RoAb18 | mAb | ECL2 | K171, E172, W190 | Inhibition of CCR5-mediated cell fusion Inhibition of CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL5/RANTES binding Inhibition of cell activation (no Ca++ flux) Block of R5-HIV strains | |
Natural anti-CCR5 Abs | Healthy donors Delta32+/+ CCR5- ESNHIV-positive | ECL2 N-term | Unknown within R168-K197 sequence | Competition for chemokine binding Binding to native CCR5 on PBMC Block of R5-HIV laboratory and primary isolates | |
Natur alanti-CCR5 Abs | ESN LTNP | ECL1 | D95, F96 A95, A96 (gain of function) A89, A103 (loss of function) | Inhibition of CCL4/MIP-1beta chemotaxis Binding to native CCR5 on PBMC CCR5 downregulation Block of HIV transcytosis across membranes Block of R5-HIV isolates from A, B, C, E clades |