Structural and functional mapping of immunoglobulin V-regions

Abstract

V-regions of immunoglobulins chains contain 3 types of positions, which are equally represented: invariant and sub-group characteristic, which account for the "framework" and hypervariable positions, responsible for antigen recognition. The 3 types of positions are grouped and fall within a very few discrete stretches. Sub-group characteristic segments containing one of the 2 cysteyl residues of the V-regions may be isolated by high voltage paper electrophoresis and provide a basis to type for sub-groups in the VK and in the VH human systems. This allowed to characterize a large set of human myeloma proteins that were used in a series of competitive hybridizations which indicated that sub-groups had no influence on preferential reassociations, which occurred in 80% of the cases. This preference seems to rely mostly on individual structural differences, which may be linked to heterogeneity at the framework level. Distinction between framework heterogeneity and hypervariable regions heterogeneity may be approached by raising antibodies against a mouse myeloma protein, MOPC 173, of known sequence, by means of syngeneic and allogeneic immunizations, using Balb/c and A/J mice. Junction of distinct portions of immunoglobulin chains such as the V and the C regions raises the possibility that some recognition signals may operate at the DNA level. Since rotational symmetry regions in the DNA are known to act as such signals, it is discussed whether such regions can be expected from the amino acid sequence data, especially in the vicinity of the "switch" peptide.