Idiotypes specificities

Levitsky, H.I. et al., Immunization with granulocyte-macrophage colony-stimulating factor- transduced, but not B7-l-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity, J Immunol, 156, 3858, 1996. 

There is also considered to be a population of T suppressor cells which acts to down-regulate both T helper cells and B cells, whether through antigen-specific or idiotype-specific mechanisms. The epitopes on the lymphocyte receptor (id-iotype) recognized by the receptor on another lymphocyte (anti-idotype) can form a network of interactions through which suppression may be mediated. 

Kuettner, M.G., Wang, A.-L., Nisonoff, A. (1972). Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J. Exp. Med.135,579-595. 

Manser, T. Gefter, M.L. (1986). The molecular evolution of the immune response idiotype-specific suppression indicates that B cells express germ-line-encoded V genes prior to antigenic stimulation. Eur. J. Immunol. 16, 1439-1444. 

Pawlak, L.L., Mushinski, E.B., Nisonoff, A., Potter, M. (1973). Evidence for the linkage of the IGCH locus to a gene controlling the idiotypic specificity of anti-p-azophenylarsonate antibodies in strain A mice. J. Exp. Med. 137,22-31. 

Idiotypic specificity—Antibodies and myeloma globulins of a given specificity show differences in antigenic specificity ascribable to differences in sequence in the variable regions of their light and heavy chains. Some of these idiotypic determinants are inhibitable by the antigenic determinant or ligand for which the antibody or myeloma protein is specific, whereas others are not. Those idiotypic determinants which are inhibitable are hypothesized to in-... 

Five of the phosphocholine mouse myeloma H chains have Asx 31 while the remaining three and the human protein have Asp. Position 31 is seen to be a surface residue. If the remaining five proteins with Asx are found also to have Asp, it will probably not be in idiotypic4 determinant since the different phosphocholine-binding myeloma proteins have distinct idiotypic specificities although it could also exert a conformational role on other residues in the CDR. 

At present since there is no information associating any amino acid residue at any position in VL or VH with idiotypic specificity, the only correlations which appear possible are those in which specificity differences in antibody combining sites may be ascribable to individual residues or to groups of residues. 

A mouse model of lymphoma was used in pre-clinical studies to validate the vaccination procedure using a tobacco-derived idiotype-specific single-chain variable region fragment of the immunoglobulin from the cancerous mouse B-cell lymphoma [236]. Non-vaccinated mice died within 3 weeks of tumor injection, while 80% of the vaccinated mice were protected from the cancer and survived. 

G. Linkage of Genes Controlling Allotypic and Idiotypic Specificities... 

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). 

Many monoclonal IgM proteins which have anti-IgG activity are cryoglobulins that is, they fail to precipitate with IgG at 37°C but do form precipitates at lower temperatures. The IgM antiglobulin can be dissociated from the IgG in the precipitate by gel filtration at low pH. Such IgM proteins are often structurally related and have been studied extensively from the standpoint of idiotypic specificity and amino acid sequence (Chapter 11, Section II). 

A number of different mouse myeloma proteins [IgA(/f)] have the capacity to bind phosphorylcholine (77,92-94). There is evidence that some of these proteins, which arose independently in different mice, may be very similar or identical in structure. This evidence includes idiotypic specificity and partial sequence analyses (Chapter 11). These proteins also react with pneumococcal type C polysaccharide, which contains haptenic determinants resembling phosphorylcholine. There exist other mouse myeloma proteins which are also reactive with phosphorylcholine but which differ in structure, as shown by differences in their idiotypic determinants, affinities for various haptens related to phosphorylcholine, and partial amino acid sequences. Leon and Young (92) recognized three classes of myeloma proteins with antiphosphorylcholine activity. Class 1 is characterized by a fairly high affinity for choline as well as phosphorylcholine the other two classes do not combine well with choline. Classes 2 and 3 are distinguished by differences in affinity for phosphonocholine. Leon and Young identified four proteins in class 3 all of these had previously been shown by Potter and Liebermann (77)... 

Myeloma proteins with antibody activity have in some instances been found to share idiotypic specificity and amino acid sequence with induced antibodies reactive against the same antigen. This is perhaps the strongest evidence for the essential identity of myeloma proteins and antibodies. 

It seems quite certain that immunoglobulin molecules synthesized by a single clone of cells share idiotypic specificity. It does not follow, however, that all molecules which share idiotype are identical in structure. For example, molecules of different classes (e.g., IgG and IgM) can have common idiotypic specificities. In such molecules the V regions must be very similar or identical although the Ch regions obviously are not. In addition, there can be microheterogeneity within V regions of molecules of the same class i.e., differences in amino acid sequence that... 

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