Mechanisms of antibody diversity: Multiple genes encode structurally related mouse κ variable regions

The complete amino acid sequences of the variable regions of three mouse Vκ-21 kappa chains (A22, T111, and CB101) and one partial sequence (B32) have been determined and are compared to four previously reported Vκ-21 variable regions. These eight κ variable region sequences have, with the exception of an amide difference at residue 1, identical amino-terminal 23-residue sequences, all are of the same length, and all have extensive amino acid sequence homology throughout the variable region. When these eight variable regions are grouped by sequence homology, five different groups (Vκ-21A, B, C, D, and E) are present whose members share common sets of amino acids within a group. Three groups of similar homology each contains at least two members (M63 and AB22 in Vκ-21B; M321 and T124 in Vκ-21C; and M70 and B32 in Vκ-21A). The repetition of these five characteristic subgroup sequences in this relatively small sample indicates that these subgroups are isotypes which are controlled by separate germline genes. It is unlikely that these sequences could have been randomly somatically generated in different animals from a single germ-line gene (parallel mutation). Although a limited number of comparisons are available, the sequence differences within the Vκ-21A, B, and C isotypes are limited to complementarity-determining regions and may have resulted from somatic mutations. The κ chains comprising the Vκ-21 isotypes offer a unique opportunity to compare the genetic interpretations of the primary amino acid sequence data with the nucleic acid hybridization data.