Variable region gene utilization and mutation in a group of neutralizing murine anti-human immunodeficiency virus type 1 principal neutralizing determinant antibodies

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Abstract

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(K)21 gene and J(K)2. These three mAbs also share the same V(K)J(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(H)4, 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(K)21-J(K)2, and BAT123 also uses the SB32V(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 he restricted to a small subset of V(H) and V(L) gene elements.

Original languageEnglish (US)
Pages (from-to)41-49
Number of pages9
JournalAIDS Research and Human Retroviruses
Volume9
Issue number1
StatePublished - 1993

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Neutralizing Antibodies
HIV-1
Mutation
Monoclonal Antibodies
Genes
Immunoglobulin Variable Region
Immunoglobulin Genes
Gene Rearrangement
Southern Blotting
Antibody Formation
Light
Amino Acids
Peptides
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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title = "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 (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(K)21 gene and J(K)2. These three mAbs also share the same V(K)J(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(H)4, 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(K)21-J(K)2, and BAT123 also uses the SB32V(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 he restricted to a small subset of V(H) and V(L) gene elements.",
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T1 - Variable region gene utilization and mutation in a group of neutralizing murine anti-human immunodeficiency virus type 1 principal neutralizing determinant antibodies

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N2 - 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(K)21 gene and J(K)2. These three mAbs also share the same V(K)J(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(H)4, 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(K)21-J(K)2, and BAT123 also uses the SB32V(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 he restricted to a small subset of V(H) and V(L) gene elements.

AB - 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(K)21 gene and J(K)2. These three mAbs also share the same V(K)J(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(H)4, 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(K)21-J(K)2, and BAT123 also uses the SB32V(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 he restricted to a small subset of V(H) and V(L) gene elements.

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