Studies on the Mechanism of Isoantigenic Variant Formation in Heterozygous Mouse Tumors. I. Behavior of H-2 Antigens D and K: Quantitative Absorption Tests on Mouse Sarcomas2

Abstract

Previous studies on the MSWB sarcoma of (A × A.SW)F₁ origin have shown that its cells contained antigens D and K of the H-2 system. It was possible to select isoantigenic variants in appropriate animal hosts. These hosts either lacked K but contained D, or lacked D but contained K. There were two types of variants isolated, as judged by their transplantation characteristics—they either behaved as if they had lost K and still contained D, or had lost both D and K. It was impossible to isolate a third type, which behaved like it had lost D but still had K. This paper extends these results to 3 tumors of (A × A.SW)F₁ origin and 2 of (A × A.CA)F₁ origin. A total of 33 variants was isolated. The transplantation data were in full agreement with the previous preliminary findings. Furthermore, the variants were analyzed for the actual presence of antigens D and K in their cells by a quantitative absorption technique. The serologic analysis completely agreed with the expectations based on the transplantation tests. For correct interpretation of the data, it was essential to exclude possible antigenic contribution of host cells. This was done by using newborn, irradiated hosts containing neither D nor K. One possible explanation of these findings is that isoantigenic variant formation is based on a mechanism involving mitotic crossing over, but further studies are required to establish this definitely.