COMPLETE SEQUENCE OF MURINE MONOCLONAL IMMUNOGLOBULIN MOPC 173 (IGG2A) - GENETIC IMPLICATIONS

  • 1 January 1976
    • journal article
    • research article
    • Vol. C127  (5) , 607-631
Abstract
The complete amino acid sequence of the murine monoclonal immunoglobulin [Ig] MOPC 173 (IgG2a, .kappa.) is reported. The H chain contains 447 amino-acid residues, and 1 carbohydrate prosthetic group attached to the ASX residue 299. The .kappa. L chain is composed of 214 residues. The H chains are covalently linked by 3 interchain disulfide bridges. The H-L bond-forming cysteine of the H chain is between the VH [H chain variable region] and the CH1 [H chain constant region 1] domain. Intrachain bridges are disposed linearly, according to the classical model. There is no simple relationship between the primary structure and any given function of a particular domain. This is presumably due to the fact that the selection pressure exerts itself on the 3-dimensional structure which may retain a conserved general organization as a result of balanced multiple mutations. Selection seems to act in 2 ways: horizontally, in a multigene system, and vertically, in which case strictly homologous domains appear extremely conserved between distinct animal species. Conservation of the VH domains seems just as high as conservation of the CH domains. The VH region contains 3 types of positions: invariant, subgroup characteristic and hypervariable. Murine V.kappa. domains, although basically built according to the same pattern, show a much more marked polymorphism of the framework, which might necessitate a higher number of basic germ-line genes. A hypothetical model of the switch mechanism is proposed. Rotational symmetry regions can be deduced at the DNA level from the known amino acid sequences of the switch peptides for the 3 translocational systems: H, .kappa. and .lambda.. These would provide recognition signals for restriction-like enzymes such as those which operate in prokaryotes. An implication of this model is the definition of an exact limit between the V and the C regions of all Ig chains.