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 (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.
Hamatake
Makiko
M
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Komano
Jun
J
Urano
Emiko
E
Maeda
Fumiko
F
Nagatsuka
Yasuko
Y
Takekoshi
Masataka
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015704:CD4 Antigens / Q000276:immunology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M