[The primary structure of a monoclonic immunoglobulin-L-chain of subgroup IV of the kappa type (Bence-Jones protein Len.)]

The complete amino acid sequence of Bence-Jones protein Len. was established by sequential analysis of tryptic and chymotryptic peptides. The result of these experiments and the comparative sequence analysis with the other 17 completely determined kappa-proteins is incompatible with the serological typisation of protein Len. as a member of subgroup II: There are 18 positions in protein Len. than cannot be associated with any one of the subgroups kappaI, kappaII or kappaIII. Also the average amino acid exchange rate between protein Len. and these subgroups is in the same range as the average amino acid exchange rate between these subgroups. Therefore Bence-Jones protein Len. is the first completely determined representative of a new IV. kappa-type subgroup. The variability of immunoglobulins follows a structural principle in which the single point mutations responsible for the variability are linked. The present paper contains the exact analysis of the linked point mutations within the so far best-investigated subgroup, kappaI (12 completely sequenced proteins). These linked exchanges allow the arrangement of the kappaI proteins in 4 subgroups and their further subdivision. The regularity of this amino acid sequence pattern can only be explained by an evolutionary origin of antibody variability. On the basis of this evolutionary mechanism the relationship of immunoglobulins can be depicted in a phylogenetic tree. Such a tree was therefore constructed for the 18 completely determined Bence-Jones proteins of kappa-type, for the first time taking into account Bence-Jones protein Len. Its topology is in complete agreement with the results of the comparative sequence analysis.