Variable region subgroups

Forre et aL (1976) have developed subgroup-specific antisera to human myeloma heavy chains. The antisera were developed from heavy chains whose variable region amino acid sequences were known, thus providing a primary structural basis for the serology. A survey of 167 nonsequenced myeloma proteins showed a ratio of 1 2 3 for VhI VhII VhIII. This same group (Forre et aL, 1977) has detected Vh determinants on the surface of lymphocytes from patients with chronic lymphocytic leukemia. The number of patients studied is too small to allow conclusions to be drawn about distribution of Vh subgroups on the cell surface. 

The variable regions of both k and X chains can be divided into subgroups, according to homologies in amino acid sequence. These subdivisions are based on sequences of L chains of myeloma proteins and of Bence Jones proteins. Kappa chains fall naturally into three major subgroups on the basis of the length of the variable region and the presence of certain amino acids at particular positions in the sequence. ... 

Fig. 4.2. Amino acid sequences in the variable regions of human k chains, k, is divided into subgroups, la and Ib, according to Milstein and Deverson (25). Amino acids which are characteristic of the V i subgroup (not necessarily present in all members of the subgroup) are indicated by an asterisk in the prototype sequence. The format used is described in footnote 1. Note that six insertions are needed to provide homology between residues 31 and 32 in Van- References protein Roy (4) Ag (153) Bel (154) Hau (155) Ou (156) Eu (2) Dee (25) Dav and Fin (42) Cum (157) MU (158) Ti (159) B6, Fr4, and Rad (160) human pool (29). The subgrouping Van and Vani is that used by Hilsch-mann, Capra, and Milstein and Pink it is reversed in some of the earlier literature. Additional sequences are listed in references 35, 59, and 160a. A solid line represents identity of sequence with the prototype for that subgroup (proteins Roy, Cum, or Ti).

The exact position of the responsible subgroup-associated antigenic determinants within the heavy-chain variable domain is not yet clear. It seems obvious that they are not likely to be associated with the hypervariable regions (see below). Very probably they do involve, at least... 

Many positions in the V, regions are neither invariant nor hypervariable but, within a subgroup, show a moderate frequency of variation. The nature of this variability can best be understood by referring to amino acid sequences tabulated in Chapter 4. Usually, differences outside hypervariable regions, within a subgroup, are associated with a single base change in the DNA sequence. 

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