Antigenic Characterization of Heterozygous Mouse Lymphomas After Immunoselection In Vivo2

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Abstract
Previous studies on the isolation and characterization of isoantigenic variants from heterozygous mouse tumors derived from F1 hybrids of two congenic resistant mouse strains, differing at the histocompatibility-2 (H-2) locus, have been extended to two Moloney virus-induced lymphomas induced in (A × A.CA)F1 mice (H-2a, H-2f). Five antigenic markers were studied: components 3, 4, 5, and 11, determined by the H-2a complex and component 9 of H-2f derivation. The antigenic behavior of the two lymphomas and variants, derived by selective propagation in mouse genotypes deficient in one or several of the antigen markers, was studied by transplantation, cytotoxicity, and membrane fluorescence tests. The three tests agreed well. Selection against a whole H-2 antigen complex, derived from one parental strain, by propagation in the opposite parental strain, led to the loss of all antigens specifically derived from the complex subjected to negative selection, in agreement with previous findings. Selection against parts of the H-2 complex gave different results, depending on the system. Selection against 5 and 11 led to the disappearance of 3, 5, and 11. The loss of 3 and 5 was reversible, however, under certain conditions of further, permissive propagation. The −3, +4, −5, −11, +9 variant could lose 9 on further selection against the A.CA complex. The arising −3, +4, −5, −11, −9 line was the “minimum” antigenic variant obtainable. Further selection against 4 was unsuccessful, and it was not possible to “switch” the established +4 variants to the opposite compatibility (−4, +9) or to obtain “zero” variants by prolonged passage in newborn and/or irradiated A.CA mice. It was equally impossible to switch established −4, +9 variants to the opposite, +4, −9 type. Further studies on the interrelation of the various H-2 antigens in selective systems of this type may yield information about the synthetic, structural, and functional interrelationships of the various H-2 components.

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