Variable Region Gene Utilization and Mutation in a Group of Neutralizing Murine Anti-Human Immunodeficiency Virus Type 1 Principal Neutralizing Determinant Antibodies

The heavy (V_H) and light (V_L) chain variable region nucleotide sequences of four neutralizing anti-human immunodeficiency virus type 1 (HIV-1) murine monoclonal antibodies (mAbs) were determined. These mAbs bind to native gp120, recombinant gp120, and a linear HIV-1 principal neutralizing determinant (PND) peptide that spans amino acid 308-328. Three mAbs that bind to the same linear determinant, 110.3, 110.4, and 110.5, all use the same V_L gene elements, a V_K21 gene and J_K2. These three mAbs also share the same V_KJ_K junctional diversity and specific somatic mutations. They have identical V_L immunoglobulin gene rearrangement patterns on Southern blot. Two of the antibodies, 110.4 and 110.5, also use the same V_H gene elements, SB32-D-J_H4, and have identical VD and DJ junctions and N sequences. Two different anti-HIV-1 PND murine mAbs reported by others, BAT123 and 0.5β, also use V_K21-J_K2, and BAT123 also uses the SB32 V_H gene element. Although 110.3 uses the same V_L region gene as 110.3 and 110.4, it uses a different V_H gene that appears to be a member of the 7183 V_H family. 110.6, an mAb that recognizes a discrete, overlapping PND compared to 110.3, 110.4, and 110.5, uses entirely different V_H and V_L gene elements and has unique immunoglobulin V_H and V_L rearrangement patterns. Our data, taken together with reports of the BAT123 and 0.5β mAb sequences, suggest that the murine antibody response to HIV-1 PND may be restricted to a small subset of V_H and V_L gene elements.