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

Abstract

The heavy (VH) and light (VL) 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 VL gene elements, a VK21 gene and JK2. These three mAbs also share the same VKJK junctional diversity and specific somatic mutations. They have identical VL immunoglobulin gene rearrangement patterns on Southern blot. Two of the antibodies, 110.4 and 110.5, also use the same VH gene elements, SB32-D-JH4, and have identical VD and DJ junctions and N sequences. Two different anti-HIV-1 PND murine mAbs reported by others, BAT123 and 0.5 beta, also use VK21-JK2, and BAT123 also uses the SB32 VH gene element. Although 110.3 uses the same VL region gene as 110.3 and 110.4, it uses a different VH gene that appears to be a member of the 7183 VH family. 110.6, an mAb that recognizes a discrete, overlapping PND compared to 110.3, 110.4, and 110.5, uses entirely different VH and VL gene elements and has unique immunoglobulin VH and VL rearrangement patterns. Our data, taken together with reports of the BAT123 and 0.5 beta mAb sequences, suggest that the murine antibody response to HIV-1 PND may be restricted to a small subset of VH and VL gene elements.