Antibodies can recognize a large number of molecular determinants (antigens) because of the diversity present in antibody combining sites. This diversity resides in regions of extensive amino acid variability termed variable (V) regions. Variable region diversity is encoded in multiple germline variable region genes and can also arise from somatic modification of these genes. An important class of somatic modifications is the rearrangement of gene segments to form complete variable region genes. In this way complete VL genes arise from the joining of VL and JL gene segments while VH genes arise from VH, D, and JH gene segment joining.
Studies of the V region protein sequences of hybridoma and myeloma immunoglobulins which bind phosphorylcholine show that IgM antibody V regions are considerably less diverse than IgG and IgA V regions. A comparison of protein sequence data with experiments on germline DNA suggests that at least some V segment diversity in IgG and IgA antibodies is the result of somatic mutations. D segments from phosphorylcholine-binding IgM antibodies as well as from IgG and IgA antibodies show extensive amino acid interchanges and size differences. In addition, diversity in the antibody response to phosphorylcholine is generated by associating a single VH region with at least two different VL regions.
The complete sequences of the V L and V H regions from two antibodies binding β (2 → 1) levan have also been determined. A comparison of these sequences to protein sequence data from other β (2 → 1)) levan-binding proteins and to a germline DNA sequence suggests that the levan-binding proteins may arise from multiple germline genes differing at the protein level by only a few amino acids. Unlike the D segments of the phosphorylcholine binding proteins, the levan-binding immunoglobulin D segments show very little diversity. In addition, the protein sequences of levan-binding immunoglobulins can be compared to published V region idiotype and antigen binding studies. These comparisons show that idiotypes may focus on certain sections of antibody V regions, and hence be of limited value as a probe of antibody V region fine structure.
