Preferential use of a H chain V region in antitumor-associated glycoprotein-72 monoclonal antibodies

• Published in: The Journal of immunology (1950) Vol. 151; no. 11; pp. 6559 - 6568
• Main Authors: Rixon, MW, Gourlie, BB, Kaplan, DA, Schlom, J, Mezes, PS
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01-12-1993; American Association of Immunologists
• Subjects: Amino Acid Sequence; Animals; Antibodies, immunoglobulins; Antibodies, Monoclonal - genetics; Antibodies, Neoplasm - genetics; Antigens, Neoplasm - immunology; Base Sequence; Biological and medical sciences; DNA - chemistry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Immunoglobulin; Glycoproteins - immunology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Mice; Mice, Inbred BALB C; Molecular immunology; Molecular Sequence Data; Monoclonal antibodies; Polymerase Chain Reaction; Heavy peptide chain; Tumor associated antigen; Nucleotide sequence; Variable region; Rodentia; Sequence alignment; Homology; V Segment; Glycoproteins; Monoclonal antibody; Vertebrata; Specificity; Mammalia; Mouse; Immunologic repertoire; Comparative study
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.151.11.6559

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.