Inhibition of HIV replication by a CD4‐reactive Fab of an IgM clone isolated from a healthy HIV‐seronegative individual

HIV replication is restricted by some anti‐CD4 mouse mAb in vitro and in vivo. However, a human monoclonal anti‐CD4 Ab has not been isolated. We screened EBV‐transformed peripheral B cells from 12 adult donors for CD4‐reactive Ab production followed by functional reconstitution of Fab genes. Three independent IgM Fab clones reactive specifically to CD4 were isolated from a healthy HIV‐seronegative adult (∼0.0013% of the peripheral B cells). The germ line combinations for the VH and VL genes were VH3‐33/L6, VH3‐33/L12, and VH4‐4/L12, respectively, accompanied by somatic hypermutations. Genetic analysis revealed a preference for V‐gene usage to develop CD4‐reactive Ab. Notably, one of the CD4‐reactive clones, HO538‐213, with an 1×10−8 M dissociation constant (Kd) to recombinant human CD4, limited the replication of R5‐tropic and X4‐tropic HIV‐1 strains at 1–2.5 μg/mL in primary mononuclear cells. This is the first clonal genetic analysis of human monoclonal CD4‐reactive Ab. A mAb against CD4 isolated from a healthy individual could be useful in the intervention of HIV/AIDS.