Additive Effect of Multiple Weak Incompatibilities in Transplantation Immunity

Abstract

BOTH synergistic and antagonistic effects of immunization with multiple antigens have been reported in general immunology. The same has been difficult to examine in transplantation immunity because the frequently used strains of mice usually differ by multiple antigenic factors, including those controlled by the ‘strong’ H-2 locus. (Reference to gene ‘strength’ in the present context pertains to the effects of the antigenic products of the particular gene on graft survival and should not be confused with the more common genetic use of the word to indicate relative dominance or recessiveness. All known histocompatibility genes are dominant.) With strains differing by the antigens of one and two weak genetic factors it was possible to demonstrate shorter graft survival when two incompatibilities were present. The mice used were progeny of pedigreed pairs obtained from George Snell of Bar Harbor, Maine^1,2, and were the products of brother–sister matings carried out in such a way that no experimental mice were more than two generations apart. The strains used, along with their genetic relationships, are shown in Table 1. It will be noted that the three strains are identical at the H-2 locus, that B10 and B10.129 (5M) differ only at H-1, that B10 and B10LP differ only at H-3 and that B10.129 (5M) and B10.LP differ at both H-1 and H-3.