Inhibition of HIV replication by a CD4‐reactive Fab of an IgM clone isolated from a healthy HIV‐seronegative individual
| Autor: | Fumiko Maeda, Jun Komano, Yasuko Nagatsuka, Emiko Urano, Masataka Takekoshi, Makiko Hamatake |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Herpesvirus 4 Human medicine.drug_class Somatic cell Immunology Biology Virus Replication Monoclonal antibody Peripheral blood mononuclear cell Autoimmune Diseases law.invention Immunoglobulin Fab Fragments Antibody Specificity law HIV Seronegativity medicine Humans Immunology and Allergy Gene Cell Line Transformed B-Lymphocytes Antibodies Monoclonal Cell Transformation Viral Virology Molecular biology Immunity Innate In vitro Clone Cells Immunoglobulin M CD4 Antigens Monoclonal HIV-1 Recombinant DNA Clone (B-cell biology) |
| Zdroj: | European Journal of Immunology. 40:1504-1509 |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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