The Major Histocompatibility Complex

Abstract

At the beginning of this century, Tyzzer and Loeb showed that tumors of a strain of mice (A/A) grow normally if they are transplanted into mice of the same inbred strain (syngeneic, see Table 6.1); however, they are rejected by mice of another inbred strain (allogeneic, e.g., B/B). Mating experiments showed that susceptibility for tumor growth is genetically controlled: all F₁ animals of the cross A/A × B/B accepted tumors from both parental lines. Based on the percentage of accepted parental tumors in the F₂ generation, Little and Tyzzer calculated that in the mouse at least fifteen genes were responsible for the resistance to the parental tumor, because tumors grew in only 1.6% of the F₂ animals. According to the preceding example, if susceptibility were controlled by one gene, 75% of the F₂ animals would have been susceptible to the parental tumor tissue (50% A/B, 25% A/A, 25% B/B); if susceptibility were controlled by two genes, the number of susceptible animals would be reduced to 56% (9/16). In general, the percentage of F₂ animals in which a parental tumor grows is (3/4)ⁿ, where n represents the number of different genes of both parental strains that control susceptibility. From these findings it was determined that susceptibility was controlled by several dominant genes.