Amino acid sequence of the variable region of M149 mouse myeloma light chain: Comparison with the nucleotide sequence of K2 and K3 clones

Abstract

The complete amino acid sequence of the kappa chain variable region from M 149, a myeloma urinary protein of BALB/c origin, has been determined. This sequence is compared with sequences of kappa chains from myeloma proteins that belong to the same group. The M 149 structure is also compared with the amino acid sequence derived from the nucleotide sequences of two EcoRI fragments (K2 and K3) of mouse DNA. These DNA fragments encode variable gene sequences closely related to mouse kappa light chain M149. Comparison of the protein sequence with the nucleotide sequence reveals differences in only 13–18 residues, which are clustered both in complementarity-determining regions and framework regions. When the probe derived from M149 tumour m-RNA was hybridized with mouse genome DNA, 6–8 different bands were revealed (Seidman et al., 1978 b). Furthermore, the amino acid sequences corresponding to the K2 and K3 fragments have not yet been found among kappa light chains whose structures have been determined. These results therefore, raise the possibility that a set of genes (6–8), some of which remain silent, might exist in the mouse genome corresponding to each of the many groups identified among kappa light chains. Recent work has shown that light chain genes are encoded in three segments, a major variable region sequence, a short J sequence and the constant region sequence. Five J segments have been identified for all BALB/c mouse kappa chains by means of nucleotide sequencing of embryonic DNA (Max et al., 1979; Sakano et al., 1979). The J2 segment of embryonic DNA corresponds to the amino acid sequence, of M 149 protein covering residues 96–108.