Chemical structure of light chains.

Abstract

The light chains of immunoglobulins are a heterogeneous population of peptide chains. Two general types can be recognized immunologically and chemically, the λ and the K light chains. But within the two types further heterogeneity has been demonstrated. A minor heterogeneity observed in the K chains has given rise to two main groups known as Inv (1, 2) and (3): this is under genetic control (see Oudin—this discussion). But the most interesting heterogeneity, which gives rise to an innumerable population of different molecules, is superimposed on the above recognized classes. W hat the nature of this heterogeneity is and what is the mechanism whereby each variant is produced, are fundamental problems in understanding the immune response. The main technical difficulty in chemical studies of light chains is that so far all attempts to produce pure molecular species of light chains from normal immunoglobulins have been unsuccessful. I started using the products of the myeloma patients in the hope that structural comparison with normal chains might give indications about their relationships. The evidence obtained so far (and I will refer to some of it later) shows that the general pattern of the structure of normal and myeloma light chains is strictly comparable if one assumes that the normal light chain is an undefined pool of myeloma light chains. From the several lines of attack, we have chosen to do comparative sequence studies around the disulphide bridges of Bence-Jones proteins and light chains, as a tool to help our understanding of the nature of the variability of the light chains of immunoglobulins. So far in all the cases studied the K chains appear to contain three disulphide bridges.