Cross-idiotypic specificity

The studies of Braun and Jaton (34) also indicated that rabbits belonging to the same inbred family group frequently produce antistreptococcal antibodies with k chains of the same subgroup and with remarkably similar N-terminal sequences. In some instances such antibodies also exhibit cross-idiotypic specificity (defined in Chapter 11, Section II,A). 

Apparently related observations were made by Hannestad et al. (24) who investigated two IgM monotypic proteins with different electrophoretic mobilities, isolated from the serum of a single patient. Both proteins reacted specifically with a trinitrophenyl derivative of hemo-cyanin. The IgM proteins were not, however, identical in specificity since only one of them reacted with a Klebsiella polysaccharide. Each protein had individual, unrelated idiotypic determinants but also held in common other antigenic determinants that were not found in 99 other serums from patients with Waldenstrom s macroglobulinemia or rheumatoid arthritis. This appears, then, to be another example of cross-idiotypic specificity. 

B. Whether the proteins studied by Franklin and Frangione possessed true or cross-idiotypic specificity is uncertain since the anti-D antisera were absorbed with various immunoglobulins but not with heterologous anti-IgG cryoglobulins. 

From the studies reported so far it seems likely that proteins exhibiting cross-idiotypic specificity have L chains, H chains, or both... 

Amino acid sequence studies were carried out by Rudikoff et al. on six BALB/c IgA myeloma proteins, each of which binds j8(l 6)-d-galactan (46b) several of the proteins exhibited cross-idiotypic specificity but each had at least one unique determinant. The L chains (type k) were sequenced from the N-terminus through position 23 and found to be identical. Among the six H chains, four were identical to position 30, and the other two chains each exhibited only one substitution as compared to the four identical proteins. 

These results, together with data on idiotypic specificities in inbred mice, indicate that idiotype can be transmitted genetically. It should be noted, however, that studies of rabbit antiproteus (7), antisalmonella (8) and antipneumococcal (40c) antibodies have not revealed any pattern of cross-reactivity within a family. Why rabbits producing high titers of antistreptococcal antibodies tend to produce antibodies with shared idiotype remains to be elucidated. A similar question arises with respect to inbred mice the occurrence of strong intrastrain idiotypic cross-reactions varies with the antigen and the strain. 

Another example of idiotypic cross-reactivity between myeloma proteins and induced antibodies was reported by Weigert and his collaborators (54,55). They found that a small but significant percentage of myeloma proteins induced in BALB/c mice have antibody activity against a(l 3)dextran and share idiotypic specificity. These include an IgM as well as a number of IgA proteins all are of type X. The same idiotypic specificity was found in anti-a(l 3)dextran antibodies of all immunized, normal BALB/c mice. 

The suppressed mice produced anti-Ar antibodies in titers comparable to those of controls. Interestingly, the idiotypic specificities of the anti-Ar antibodies arising in different, suppressed A/J mice were not cross-reactive with one another (104). This result indicates that A/J mice are capable of synthesizing a large variety of antibody molecules specific for the azophenylarsonate group but that expansion of one or a few identical clones occurs in all nonsuppressed mice of that strain. 

For three other myeloma proteins having anti-(l — 6)-a-D-glucopyranan specificity (W 3129, W 3434, and QUPC 52), the authors found a somewhat different pattern of cross-reactivity.63 The reaction of W 3129 with its anti-idiotypic antibody was not totally inhibitable by even high concentrations of W 3434 protein, and not at all by protein QUPC 52. Thus, proteins W 3129 and W 3434 share some determinants, but are clearly different from each other and from QUPC 52. 

F6. Fong, S., Gilbertson, T. A., Chen, P. P., Vaughan, J. H., and Carson, D. A., Modulation of human rheumatoid factor-specific lymphocyte responses with a cross-reactive anti-idiotype bearing the internal image of antigen. J. Immunol. 132, 1183-1189 (1984). 

Guery JC, Druet E, Glotz D, Hirsch F, Mandet C, De Heer E,and Druet P. Specificity and cross-reactive idiotypes of anti-glomerular basement membrane autoantibodies in HgCl2-induced autoimmune glomerulonephritis. European Journal of Immunology 20 93-100,1990. 

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