Amino acid sequence of the variable region of a human mu chain: location of a possible JH segment.

The complete amino acid sequence of th variable (V) region of the mu heavy chain of a human IgM immunoglobulin (Cam) has been determined. The strategy for sequence determination involved sequenator analysis of the CNBr cleavage products of the succinylated carboxymethylated Fab mu fragment, and of tryptic peptides of the CNBr polypeptides and thermolytic subpeptides. The variable region of this heavy chain (VH) belongs to the VHIII subgroup; it has greater than 70% homology with other VHIII sequences and contains the VHIII marker peptide, Phe-Thr-Ile-Ser-Arg (residues 67-71). As more sequences have been published, the number of subgroup-specific residues has diminished to the point that no position is absolutely subgroup specific. An analysis of the available human VH sequences in the V/C switch region showed the likelihood of a human JH segment (residues 101-113) analogous to the J segments in mouse light chains. The JH region is highly conserved, has striking homology to proposed mouse JH regions, and has significant homology to known mouse J lambda and J kappa segments.