- Class I and II molecules preferentially activate cytotoxic T cells and helper T cells, respectively, in primary in vitro alloactivation of T lymphocytes. Collaboration between these subpopulations leads to an efficient anti-class I specific cytotoxic response. We tested whether the presence of class II, in addition to class I, alloantigens on thyroid allografts in vivo induces augmentation of anti-class I antigen immune response and leads to rejection of K/D region disparate grafts which otherwise would have been accepted. Different pairs of K or D region disparate mouse strains were selected in which transplantation across a class I antigen disparity alone resulted in long-term graft acceptance. In some pairs of mouse strains, co-transplantation of recipient mice with a second thyroid graft sharing the K/D region of the first, but additionally expressing an allo class II molecule, led to accelerated K/D region disparate thyroid graft rejection. Transplantation of thyroid allografts expressing both class II and I alloantigens did not induce increased host anti-class I antigen cytotoxic response, or affect the frequency of specific precursor cytotoxic T cells. In one pair of congenic mouse strains, acute rejection of K/D region disparate thyroid grafts occurred in the absence of class II alloantigen stimulation; in other strains, co-transplantation of class I and II alloantigen disparate thyroid allografts was not sufficient to induce K/D region disparate graft rejection. The results thus demonstrate that a class II alloantigen on a thyroid graft may augment the rejection response directed against the graft class I alloantigens. The class II alloantigen stimulation was not always essential or sufficient for induction of class I antigen disparate thyroid graft rejection, and was dependent on the specific I region and/or K/D region gene allele.