In principle, four genetic attributes of allorecognition systems govern whether the outcome of an intergenotypic interaction leads to fusion, transitory fusion, or rejection: (1) the numbers of loci that confer allotypic specificity; (2) the number of alleles per locus; (3) the allelic dosage rules that specify how many alleles two individuals share at each locus; and (4) the threshold levels of overall (i.e., multilocus) allotypic similarity necessary to produce each of the three observed outcomes.
Each iteration of this process therefore generates multilocus allotypes for two full sibships of ten progeny, and then calculates the allotypic similarity of each pair of full sibs (45 unique pairings per full sibship) as the ratio of the actual number of alleles shared to the number of possible matches.
To generate allorecognition outcomes from the simulated values of allotypic similarity, threshold proportions of overall allotypic similarity necessary to produce fusion, transitory fusion, and rejection must be superimposed on the simulated values.
Such intransitivities suggest that siblings need not share all allotypic determinants in order to be fusible (reviewed in Grosberg 1988).
However, to the extent that fusion requires a higher degree of allotypic matching than does rejection, the proportion of unique compatibility groups in a compatibility matrix need not be positively related to the level of allotypic disparity among the genotypes used to construct the matrix.
An analysis of patterns of allotypic similarity could, in principle, provide some insight into the formal genetics of allorecognition.
Thus, the mean similarity index (as calculated above) based on shared patterns of allotypic response between all pairs of full sibs is 0.75, the same as the fusion [TABULAR DATA FOR TABLE 3 OMITTED] frequency.
Although allotypic epitopes can be expressed by many IgG molecules independent of their isotype, idiotopes that are formed by the variable region on the Fab portion mostly are unique epitopes.
As confirmed by similar observations of Vaidya and Beatty (16), polyclonal murine IgG prepared from many animals seems to be the best reagent to block interferences by such HAMAs because it will present all allotypic and cross-reactive idiotypic epitopes expressed on murine IgG molecules, whereas blocking reagents based on a single monoclonal antibody, such as MAK33, can be unsuitable when they are missing the respective epitopes.
In summary, our data demonstrate that, in patients treated repeatedly with the same monoclonal antibody, a considerable percentage of the HAMA response is directed against allotypic and cross-reactive idiotypic determinants.