Faculty Bibliography

Mu-chain protein GLI is a pentameric molecule with an amino-terminal deletion comprising 130 residues. The half-cysteine residue (position 140) which forms the H-L disulfide bridge in normal IgM is present. Instead of being joined to the L chain, it presumably exists as an additional inter-H-H disulfide bridge. The kappa Bence Jones protein is of normal size and present in two forms: as monomers and dimers. The carboxy-terminal half-cysteine of the monomer is bound to cysteine. Possible reasons for failure of assembly between mu and L chains are briefly discussed.

The amino acid sequence of the heavy chain of an IgA2, AIm(1) polymeric myeloma protein (Avil) was studied. Altogether, sequence data were obtained for some 130 residues. Including the amino acids placed by homology with IgA1, this accounts for some 170 residues, thus representing more than one-third of the alpha2 chain. The sequence includes 26 amino acids from the amino-terminal end (V-H III), and 25 residues at the 'hinge' region. Of a total of 17 cysteine residues, 14 were located in regions of the molecule which were identical or homologous in the alpha1 and alpha2 chains. These striking homologies, together with the results obtained by diagonal maps of classes of IgA. Study of the cysteine-containing peptides of the J chain are consistent with the conclusion that the J chains associated with different classes of immunoglobulins are identical.

The heavy chain (gamma-3) of the IgG3 subclass of human immunoglobulins has a molecular weight of 60,000, instead of the 50,000 value reported for gamma-1, gamma-2, and gamma-4 heavy chains. By use of protein Omm, a gamma-3 heavy chain disease protein, it was possible to isolate and analyze the extra fragment. Protein Omm had a molecular weight of 40,000, glycine as its sole NH-2-terminal, and contained only the hingee region and the C-H-2 and C-H-3 domains. CNBr cleavage at Met 252 (gamma-1 numbering) yielded the hinge fraction (Fh fragment). On the basis of the molecular weight of Fh (11,000), its amino-acid composition, its partial sequence, and its unexpectedly low number of tryptic peptides, it is postulated that the extra fragment in gamma-3 heavy chains represents a series of similar or identical duplications of sections of the previously reported gamma-3 hinge region. In addition, there are striking homologies with the hinge region of alpha-1 and alpha-2 heavy chains, one of which also has duplications. The relationship of these hinge structures in different immunoglobulins supports the concept that this region is coded by a unique, small piece of DNA, which has evolved in parallel manner with the immunogolbulin genes by partial duplications and/or crossingover.

An analytical method, described herein, is based on differences in the primary structure of immunoglobulins and their subclasses. This method is independent of the supply of specific antisera, is simple and inexpensive to perform, and is fully reproducible. The distribution of subtypes of IgG and IgA resembled published results from immunological studies. Finding of differences in the distribution of subclasses of IgG proteins in patients with light-chain disease or in the absence of M-protein is of special interest.