Variable region genes of anti-HIV human monoclonal antibodies: non-restricted use of the V gene repertoire and extensive somatic mutation

Molecular Immunology
M J MoranE M Hersh

Abstract

The extent of the expressed human V gene repertoire for the most part has been derived from fetal cDNA libraries, autoantibodies, and myeloma proteins. In order to continue to explore the utilization of the VH and VL gene repertoire in response to exogenous viral antigens, the heavy and light chain cDNAs from four human anti-HIV monoclonal antibodies were PCR amplified from human-mouse heterohybridomas, cloned, and nucleotide sequence analysis performed. Of the monoclonals analyzed, three were directed against gp120 and one reacted with gp41. Three of the antibodies were of the IgG1 lambda isotype and one was an IgG1 kappa. Three of the four heavy chains were derived from VHI gene segments and one VHII was observed. D segments showed evidence of D-D joining and three JH4 and one JH5 gene were utilized. Two V lambda II lambda chains and one from the V lambda III gene family were observed and the single kappa chain sequenced was from the V kappa III family. DNA sequence comparison with known germline gene segments identified putative precursor V gene segments for one of the heavy chains and two light chains. Comparison of the expressed amino acid sequences with the predicted germline sequences indicated that changes were clustere...Continue Reading

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