Structural Correlates of Cross-reactive and Individual Idiotypic Determinants on Murine Antibodies to A-(1 ~ 3) Dextran*

Since their first description over 20 years ago, idiotypes have been used extensively to study various aspects of the immune system (1, 2). Idiotypes, antigenic determinants associated with immunoglobulin-variable regions, have been found on VH and VL regions, or both (3-11), and have been localized to both antigen-binding and framework regions (12-17). Those idiotypes shared by immunoglobulins known to be structurally different are designated IdX, 1 cross-reactive or public idiotypes, whereas those apparently restricted to one or a few closely related types of molecules are designated IdI, individual or private idiotypes. In spite of these general descriptive associations, the molecular bases for idiotypes have not been precisely defined. This lack of molecular correlation stands in striking contrast to the precise structural correlations for the constant region allotypes of rabbit and human immunoglobulins where allotype-positive and -negative proteins differ by only one or a few amino acid residues. Closely related sets of structurally defined idiotype-positive and -negative proteins have not previously been described. As part of an examination of the murine repertoire of anti-a-(1 ~ 3) dextran antibodies, a number of dextran-binding hybridoma proteins have been produced. A comparison of amino acid sequences (18) and idiotype expression of these proteins has allowed us to determine the molecular basis of anti-dextran idiotypes as a result of two features. First, the light chains from two dextran-binding myeloma proteins, MOPC104E and J558, are identical by amino acid sequence analysis. Furthermore, the light chains of these proteins and the 10 hybridoma proteins are identical by isoelectric focusing. I f these 12 light chains are identical, idiotypic variability is encoded only in heavy chains. Second, some idiotype-positive and idiotype-negative heavy chains are different by only one or a few adjacent amino acids. Accordingly, precise correlations between IdX and IdI have been made with amino acid sequence variations in certain portions of the Vrt regions.