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Title: Inhibition of HIV replication by a CD4-reactive Fab of an IgM clone isolated from a healthy HIV-seronegative individual. Author: Hamatake M, Komano J, Urano E, Maeda F, Nagatsuka Y, Takekoshi M. Journal: Eur J Immunol; 2010 May; 40(5):1504-9. PubMed ID: 20162549. Abstract: 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 (approximately 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 x 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 microg/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.[Abstract] [Full Text] [Related] [New Search]