V region subgroups

Most polypeptide chains belonging to the same V region subgroup have the same length, although exceptions occur (8,13). 

K. A Germ Line Gene for Each V Region Subgroup... 

Another focus of discussion, first considered by Doolittle (70), is the presence of amino acid residues at certain positions that are characteristic of a species. The term species-specific residue will be used to denote amino acid residues which are present at a given position in a V region (Vl or Vh) of one species but not another. In some instances a residue may be found in only one V region subgroup of a species but not at all in another species. Such a residue will still be referred to as species-specific despite its absence from some immunoglobulins of the species in which it is found. Capra et al. (71) prefer the term, phyloge-netically associated, to species-specific residue since closely related species often possess the same characteristic residue at a given position. 

Figure 1.3 Amino acid sequences of human V region subgroups. A straight line indicates that a residue is identical to that in the first sequence listed for that subgroup. ( ) Empty parentheses are gaps inserted to maximize homologies. (-) Undetermined amino acid residues. PCA, pyrrolidone carboxylic acid. Protein O/u has an insertion of four Tyr in a row at position 110. Patient Til had a biclonal gammopathy (IgG2, IgM). Both proteins appear to have the same V sequence (refs. 8-22).

Human k light chains appear to be much less diverse than murine chains. In contrast to the 24 groups of mouse VK sequences [41], the human VK sequences have been placed into four subgroups (VKI, II, III, IV) [35]. Each human VK subgroup is characterized by a set of consensus amino acid residues distributed throughout the V region. 

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. 

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).

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