Preferential use of a H chain V region in antitumor-associated glycoprotein-72 monoclonal antibodies.
The DNA sequence of the mouse H chain V regions from five hybridomas directed against the human tumor Ag tumor-associated glycoprotein-72 (TAG-72) have been determined. This includes a previously determined VH gene sequence from a first-generation anti-TAG-72 mAb, B72.3, and the VH gene sequences from four second-generation anti-TAG-72 mAb, CC49, CC83, CC46, and CC92. A sequence comparison revealed a high degree of shared sequence identity between the five productively rearranged VH genes, suggesting derivation from a common germ line V region gene. In the process of cloning the unrearranged germ line gene, two highly related VH germ line genes were identified and designated VH alpha TAG-1 and VH alpha TAG-2. A comparison of the productively rearranged anti-TAG-72 VH sequences with the two germ line VH genes demonstrated that they were all derived from VH alpha TAG-1. In contrast, the L chain V regions are all derived from separate germ line V region genes. The preferential use of VH alpha TAG-1 in these five mouse hybridomas suggests that VH alpha TAG-1 is a preferred anti-TAG-72 H V chain region germ line gene and that the H chain plays a predominant role in the recognition of this Ag.
Rixon
M W
MW
Dow Chemical Co., Central Research-Bioproducts Laboratory, Midland, MI 48674.
Gourlie
B B
BB
Kaplan
D A
DA
Schlom
J
J
Mézes
P S
PS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics*; D000912:Antibodies, Neoplasm / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D005803:Genes, Immunoglobulin; D006023:Glycoproteins / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C047052:tumor-associated antigen 72; D004247:DNA