When Ig chains were first sequenced, segments within the constant regions of H and L chains showed sequence similarities, and this led to the idea that the Ig chains had all evolved from a primordial gene coding for about 100 amino acids (1). The domains within the Ig chains all contained a characteristic intrachain disulfide bond, and the idea of the domain as an independent structural unit was proposed (2). The domain hypothesis was firmly established when the structures of V and C domains were determined to reveal a common fold forming a sandwich of two p-sheets that was stabilized by the conserved disulfide bond (3, 4). Beta-2 microglobulin (P2-m), identified in the urine of patients with kidney disease, was the first nonimmunoglobulin structure found to share sequence similarities with Ig-domains. The pz-m sequence looked like an Ig C-domain (5, 6). P2-m was subsequently discovered to be part of the major histocompatibility complex (MH C) class I structure, and sequencing of the class I heavy chain showed that a segment of sequence adjacent to the transmembrane region was also similar to Ig C-domains (7, 7a). MHC antigens were known to play some role in the specificity of T lymphocyte