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​3.3. Isotypic and allotypic variation of light chain constant domains

Chapter 3

In addition to genetic recombination and somatic hypermutation of the variable domains, further heterogeneity of light chains arises from isotypic and allotypic variation of the constant domains (Figure 3.6B and C). The human genome contains a variable number of λ constant genes, giving rise to multiple λ chain isotypes, which can be distinguished serologically by the expression of Mcg, Kern and Oz markers. Additionally, the genome contains a single κ constant gene for which three serologically-defined allotypes have been identified, designated Km1, Km2 and Km3 [92]. These allotypes define three Km alleles, which differ in two amino acids, as presented in Table 3.1. There is no evidence that these constant region variants affect FLC measurements using Freelite® assays, which are based on polyclonal antisera (Chapter 5).

Km allele Amino acids
Km1 Val(153) Leu(191)
Km1,2 Ala(153) Leu(191)
Km3 Ala(153) Val(191)

Table 3.1. Amino acid substitutions in κ light chain constant domains.

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