Allotypes

Protein macromolecules present in biological fluids are almost invariably heterogeneous in their characteristics. They may be products of more than one gene in the population (allotypes in the case of proteins isoenzymes in the case of enzymes), or a single individual (isotypes of proteins, allelozymes of enzymes), or be subject to post-translational modification. The result of this inherent molecular heterogeneity is that different forms of the same protein may behave differently with respect to... 

Fig. 11. Schematic representation of the binding properties of anti-idiotype antibodies and antimetatype antibodies. V, hapten a-Id, a-type anti-idiotype antibody /i-Id, /i-type anti-idiotype antibody Met, anti-metatype antibody anti-C-region, antibodies recognizing the constant region of a primary antibody (recognizing isotype or allotype).

Early evidence pointing to a restriction in immunoglobulin expression was the demonstration that, in individuals who are heterozygous for allotype, myeloma proteins carry one or the other, but never both, of the allelic determinants found in the pooled immunoglobulin of that person (M rtensson, 1961 Harboe et al., 1962). This finding was interpreted to indicate that the alternate allotypic determinants are present on different immunoglobulin molecules, which are produced by different cells. Oudin (1960) had observed a presumably related phenomenon in rabbits. 

In 1963, shortly after the four-chain model for immunoglobulins was proposed, Dray and Nisonoff showed that immunoglobulin molecules from rabbits heterozygous for allotypic determinants at a light chain locus contain either light chains of one allotype, or of the other, but not both. These authors did not interpret the results... 

It has been known for many years that during the course of a typical immune response, different antibody classes are produced IgM is found early in the response and IgG later (e.g. Bauer and Stavitsky, 1961 Uhr and Finkelstein, 1963). In a typical heterogeneous polyclonal response, the IgM and IgG antibodies appear to have similar specificity, but the structural relationship of the binding sites (in modern terms, the V regions) associated with these different classes cannot easily be evaluated. However, a crucial insight into the relationship among V regions of different antibody classes was provided by Todd s observation (1963) that rabbit IgG and IgM express the same a-locus allotypic determinants. 

Dubiski, S. (1969). Immunochemistry and genetics of a new allotypic specificity A 4 of rabbit yG immunoglobulins recombination in somatic cells. J. Immunol. 103,120-128. 

Kindt, T.J., Mandy, W.J., Todd, C.W. (1970). Association of allotypic specificities of group a with allotypic specificities All and A12 in rabbit immunoglobulin. Biochemistry 9, 2028-2032. 

Kipps, T.J. Herzenberg, L.A. (1986). Homologous chromosome recombination generating immunoglobulin allotype and isotype switch variants. EMBO J. 5, 263-268. 

Knight, K.L. Becker, R.S. (1990). Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes implications for the generation of antibody diversity. Cell 60,963-970. 

Knight, K.L., Malek, T.R., Hanly, W.C. (1974). Recombinant rabbit secretory immunoglobulin molecules alpha chains with maternal (paternal) variable-region allotypes and paternal (maternal) constant-region allotypes. Proc. Natl. Acad. Sci. USA 71, 1169-1173. 

Landucci Tosi, S. Tosi, R.M. (1973). Recombinant IgG molecules in rabbits doubly heterozygous for group a and group e allotypic specificities. Immunochemistry 10,65-71. 

Oudin, J. (1960). Allotypy of rabbit serum proteins. I. Immunochemical analysis leading to the individualization of seven main allotypes. J. Exp. Med. 112,107-124. 

Pemis, B., Chiappino, G., Kelus, A.S., Gell, P.G.H. (1965). Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues. J. Exp. Med. 122,853-876. 

This assay is useful because the specificity of the response to a particular antigen can be determined by using various combinations of responder cells and target cells of the Thy-1.1 or Thy-1.2 allotype. The specificity of this assay for Thy-1 has been previously described to us (3,11) and by others (12,13). 

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