SIMILARITIES IN THE LIGHT CHAINS OF ANTI-γ-GLOBULINS SHOWING CROSS-IDIOTYPIC SPECIFICITIES

Abstract

Recent studies have indicated the presence of cross-idiotypic determinants among monoclonal IgM proteins possessing anti-T-globulin activity that were not found among IgM proteins lacking this activity (1). The pattern obtained was very similar to that previously described for the IgM cold agglutinins (2) with antigenic specificities in proteins from different individuals which appeared to relate to the combining specificity of these proteins toward their respective antigens. Evidence was obtained both for the cold agglutinins and the anti-T-globulins that the antigen-combining site was involved in these specificities. Through the use of the idiotypic antisera which showed crossspecificity, it was possible to delineate two entirely separate groups of anti-Tglobulins (1). One, the major Wa group, made up approximately 60 % of the anti-'y-globulins; the other, the minor Po group, included approximately 20 % of the total; a few anti-T-globulins could not be classified in either of these two groups.The relative role of the H and L chains of these proteins in the cross-specificities was not readily determined because the antigenic determinants involved required the combination of the chains for expression. However, amino acid sequence studies on the minor Po group of anti-3,-globulins demonstrated an extraordinary similarity in H chain sequence through two hypervariable regions (3) ; the L chains were quite distinct. This suggested that heavy chain similarities were primarily involved in the cross-specificity determinants of the minor Po group. The present studies were carried out to define these relationships further by both antigenic and sequence analyses with special emphasis on the major Wa group of anti-~-globulins. A marked similarity in the L chains of this group was found. Materials and MethodsThe IgM anti-T-globulins utilized in this study were the same as those described in a previous report (1). They were initially purified in most instances as cryoglobulins from sera where they appeared as monoclonal bands; a combined procedure using Pevikon electrophoresis and Sephadex columns as described previously (1) was then utilized for final isolation. All of the proteins precipitated with aggregated Fr II 3'-globulin and this was the primary method of

Clonal nature of the immune response to phosphorylcholine (PC). V. Cross-idiotypic specificity among heavy chains of murine anti-PC antibodies and PC-binding myeloma proteins.

“…Among human IgM proteins with anti--y-globulin activity (6,10,11) and among rabbit and mouse antistreptococcal carbohydrate antibodies (4,5,7,31), cross-idiotypic determinants are more strongly associated with the antibody combining site and/or hypervariable regions than with other portions of the variable regions. These conclusions are based on a variety of data, including similarity in specificity for a particular antigen, antigen or hapten inhibition of binding to idiotype and sequence similarity of hypervariable regions in immunoglobulins in which the remainder of the variable region is virtually identical to a number of other idiotypically unrelated proteins .…”

“…In other instances of cross-idiotypy, attempts to find activity on isolated H or L chains have been unsuccessful (4, 8, 9, see 30), and instead, have relied on structural studies to associate a cross-idiotypic determinant with a particular polypeptide chain (see 10,31,32) . Recently, Thunberg and Kindt (4) have successfully employed heterologous recombinant molecules to localize an idiotypic determinant.…”

Lymphoproliferation in primary sjögren's syndrome. evidence of selective expansion of a b cell subset characterized by the expression of cross‐reactive idiotypes

“…The same families of V, and V, genes are frequently used in a proportion of patients with essential mixed cryoglobulinemia, Waldenstrom's macroglobulinemia, and CLL (26,(33)(34)(35)(36)(37). The leukemic cells in CLL express the CD5 molecule and produce autoantibodies; the same subpopulation of B cells is found in increased numbers in peripheral blood and salivary gland samples from patients with primary SS (38-40).…”

Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57BL/ka allotype.

“…Though no data on heavy chain structure have been presented, amino acid sequence analysis of the light chains from 6 of 10 cold agglutinins showed minimal differences among them (46) . Likewise, antigamma globulins selected for similarity in shared idiotypic determinants exhibit remarkable structural similarities in either their light or their heavy chains (47) . However, no two proteins appear to be completely identical in either structure or in individual antigenic specificity .…”