NUCLEOTIDE-SEQUENCE ANALYSIS OF A HUMAN MONOCLONAL-ANTIBODY-22-13 REACTIVE WITH LUNG TUMOR-ASSOCIATED ANTIGEN

A human monoclonal antibody (HuMAb) 22-13 (IgG1, kappa) recognizes a c ytoplasmic antigen associated primarily with human lung tumors. This s tudy reports the primary nucleotide and deduced amino acid sequences o f the rearranged heavy and light chains of the HuMAb 22-13. This HuMAb uses a V-H gene member of the V(H)Ia gene family, 51P1 and is product ively rearranged with a D-D fusion product of the D(LR)2 and D(XP)2 ge rm line D-H genes and the germ line J(H)3 gene. HuMAb 22-13 V-kappa be longs to the kappa light chain variable subgroup IIIb family and appea rs to be derived from the Humkv325 germ line gene and is rearranged wi th a germ line J(kappa)5 gene. The results reveal that production of a HuMAb 22-13 is achieved by rearrangement of the 51P1/Humkv325 germ li ne variable region gene combination, associated with the autoimmune re pertoire and that HuMAb 22-13 has a striking sequence homology to rheu matoid factors (RFs) of the Wa idiotypic family. HuMAb 22-13 and Wa RF s have in common V(H)Ia and V(kappa)IIIb gene segments, but use differ ent D-H, J(H) and J(kappa) gene segments. However, in spite of this st ructural similarity, HuMAb 22-13 does not display rheumatoid factor ac tivity. Taken together with the reported findings, these data indicate the representation of the shared usage of highly homologous variable region genes in entirely different humoral immune responses in the hum an system. (C) 1998 Elsevier Science B.V. All rights reserved.