Inhibition of HIV replication by a CD4-reactive Fab of an IgM clone isolated from a healthy HIV-seronegative individual. - Related Articles
Inhibition of HIV replication by a CD4-reactive Fab of an IgM clone isolated from a healthy HIV-seronegative individual.
Eur J Immunol. 2010 Feb 16;
Authors: Hamatake M, Komano J, Urano E, Maeda F, Nagatsuka Y, Takekoshi M
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, bearing 1 x 10(-8) M dissociation constant (Kd) to rhCD4, limited the replication of R5-tropic and X4-tropic HIV-1 strains at 1-2.5 mug/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.
PMID: 20162549 [PubMed - as supplied by publisher] [PubMed-HIV]