The Origin of the Immune System

It has been suggested that the neural cell adhesion molecules (N-CAM) are members of the Ig superfamily. We have examined structural homology between the N-CAM and other superfamily molecules in detail. The Ig-like domains of N-CAM have overall sizes similar to those of Ig constant domains or major histocompatibility complex (MHC) domains. Significant sequence homology was found between the N-CAM Ig-like domains and several other Ig superfamily members, such as T4, T8, IgA transport receptor, Ig VH, Ig C mu 4, and others. A comparison of the second domain of T4 (255 amino acids) with the central domain of N-CAM (302 amino acids) has demonstrated a significant sequence homology. Furthermore, a cell adhesion protein, cs-A, of slime mould, Dictyostelium, also seems to be related to N-CAM. It appears that the Ig superfamily of the immune system originated from more ubiquitous cell recognition molecules which are common in all metazoan species.