Variation allotypic

Allotypy has been studied most extensively in the rabbit, man, and mouse. In each species allotypic variation is seen in both H and L chains. In the rabbit and in man, for which data are available, genes controlling allotypic determinants on H and L chains are unlinked. In the mouse, allotypic variability of L chains has been detected by peptide mapping but, so far, not through antigenic analysis. 

Allotypic markers have been found on H chains of human IgG, IgM, and IgA and on k chains, but not as yet on the H chains of IgD or IgE or in human X chains. In each instance, antiserum has been used for the initial classification, but more recent studies have related a number of allotypic variations to differences in amino acid sequence. With one probable exception, allotypic differences attributable to carbohydrate have not been reported. All allotypic markers so far identified in human immunoglobulins are present in Ch and Cl regions. 

Residues 81-85 of the heavy chain, which Capra and Kehoe (1974) considered hypervariable in human heavy chains, are not part of the antibody combining site. They lie in a region exposed to solvent. Residues 84 and 85 are involved in a allotypic specificity in the rabbit (Mage, 1977), and the variation in the human VH chains may be associated with some function other than site complementarity. 

Paterson, T., J. Innes, L. McMillan, I. Downing, and M.C. Carter, Variation in IgGl heavy chain allotype does not contribute to differences in biological activity of two human anti-... 

In most, but not all immunoglobulins, one disulflde bond joins an H chain to an L chain. There are marked variations, however, with respect to H-H disulflde bonds. The number of such bonds, where known, is indicated by the diagrams in Table 8.1. An unusual chain structure, analogous to that found in the Azmll) allotype of human IgA2 (14,15) is observed in the IgA of BALB/c (16,16a,17) but not NZB mice (18) the L chains are disulflde bonded to one another, as are the H chains, but there are no H-L disulflde bonds. The H and L chains are therefore separable in the presence of a a dissociating agent such as 1 M acetic acid, without prior reduction of disulflde bonds. 

Additional evidence for the importance of antigenic valence is the finding of Potter et al. (34) and Potter and Lieberman (35) that Fab fragments of mouse myeloma proteins often fail to precipitate with antiidiotypic antibodies which form precipitates with the intact myeloma protein. Also, Harboe et al. (36) reported inhibition of the precipitation of monoclonal IgM by its antiidiotypic antiserum in the presence of the 7 S subunit of the IgM the latter would necessarily have a lower antigenic valence. Increased precipitability by the indirect method has also been observed in quantitative studies of certain rabbit allotypic specificities (37). The fact that Fab fragments sometimes form precipitates with antiidiotypic antibodies and sometimes inhibit precipitation is attributable to variation in the number of idiotypic determinants recognized by different antisera. 

Lymphoid tissue of animals heterozygous for either Ig locus is represented apparently by two competitively developed cell populations as a result of allelic exclusion. These populations are possibly under selection caused by certain factors. Thus, variations in the proportion of cells with different allotypes could occur. This selection is the best natural explanation of variation in the quantitative ratios of serum Ig s with the different allotypic constitutions in heterozygous individuals (Oudin, 1966). 

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