The relationship between hypervariable regions, antigen-binding specificity and the three-dimensional structure of antibodies.
The amino acid sequences of the V domains (VL + VH regions) of 3 antibodies raised to type III pneumococcal polysaccharide in individual outbred rabbits are reported. With the exception of the second hypervariable section of the L chains, these antibodies have very different sequences in the hypervariable segments of the V domains. Within the third hypervariable region of the H chain, each antibody has a different length. On the sole basis of the amino acid sequences of these three anti-pneumococcal antibodies, the results do not support the concept of a simple correlation between primary structure in the hypervariable sections (known to determine the shape of the combining site) and antigen-binding specificity. In view of the large number of amino acid interchanges in the hypervariable positions and because of the size difference between the rabbit H chains, it is likely that each anti-SIII H chain studied here represents the product of a different structural germ line gene. In contrast to such a complex immune response to a relatively simple polysaccharide antigen, an extensive structural uniformity has been observed in the heavy chains of mouse myeloma proteins with phosphorylcholine activity and a mu chain from a human Waldenström IgM endowed with the same activity. The finding of a very similar heavy chain variable region in two different species which are separated by about 75 million years in evolution favours the concept of stable transmission of variable region genes throughout evolution.
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001666:Binding Sites, Antibody; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains / Q000032:analysis; D007147:Immunoglobulin Light Chains / Q000032:analysis; D051379:Mice; D009194:Myeloma Proteins / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000276:immunology
D000906:Antibodies; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins; D011135:Polysaccharides, Bacterial