H-40, a murine histocompatibility (H)-gene linked to the Igh locus, controls the expression of a minor H antigen expressed on surface immunoglobulin positive (sIg?+?) splenic lymphoblasts and sIgM?+? B-cell tumors. Its presence on the BALB/c (Igh?a?/H-40?a?) B-cell leukemia, BCL?1?, causes its rejection in Igh?b?/H-40?b? congenic animals and the generation of anti-H-40?a? cytotoxic T lymphocytes (CTL). Since the expression of H-40 is limited to sIg?+? cells, this could be due to interaction between H-40 and Ig. We will test this possibility by modulating expression either by: (1) capping sIg; (2) inducing differentiation on sIg?-? cells; or (3) transfecting mu genes into sIg?-? cells. We will use recombinant inbred strains to further map H-40, determine its polymorphism, and define its relationship with other Igh-linked genes. A graft-versus-host (GVH) response in tumor-bearing bone marrow-transplanted recipients is sometimes associated with an antitumor effect. One possibility to explain this graft-versus-leukemia effect is that effector T cells, contained in the donor bone marrow inoculum, recognize a host minor H-alloantigen expressed by the tumor. We have shown that this possibility does not occur with the H-40 antigen. Thus, sublethally irradiated H-40?b? animals bearing an H-40?a? tumor can be protected from its lethal effects by adoptive transfer of syngeneic H-40?b? anti-H-40?a? effector T cells. However, these effector T cells do not protect sublethally irradiated H-40?a? recipients from the same H-40?a? tumor. The inability of anti-H-40?a? T cells to display an antitumor effect in H-40?a? hosts could be due to: (1) the expression of H-40?a? on normal tissues which diverts the effector cells from the tumor; or (2) because of a GVH reaction in the host donor T cells are actively suppressed. Experiments will be performed to distinguish between these two possibilities. Another mechanism by which a GVH response could induce anti-leukemic effect in tumor-bearing animals is by activating radiation-resistance host antitumor cells. This possibility will be tested by determining if mice, which have been primed so as to contain CTL precursors specific for a syngeneic tumor, display tumor resistance under conditions where they are bone marrow transplanted and subjected to GVH. The cells responsible for this resistance, both donor and host, will be determined. (AG)
| Schreiber, K L; Forman, J (1990) Effect of graft-versus-host disease on anti-tumor immunity. J Immunol 144:2018-26 |
| Schreiber, K L; Webb, C; Tucker, P et al. (1989) Developmental coupling of expression of the Igh-linked minor antigen H-40 to membrane immunoglobulin expression. Transplantation 48:331-8 |
| Cassell, D; Forman, J (1988) Linked recognition of helper and cytotoxic antigenic determinants for the generation of cytotoxic T lymphocytes. Ann N Y Acad Sci 532:51-60 |
