AKR/Cu mice have previously been reported to reject AKR/J primary lymphoma cells ( 1). The AKR/J and AKR/Cu strains are known only to differ at a segment of chromosome 9, resulting in Thy1.1 and Thy 1.2 phenotypes, respectively. Although this is the only known antigenic difference between these substrains, the Thy antigen was believed not to be responsible for tumor rejection ( 1). The present studies ( 2) document reciprocal resistance to transplantation of spontaneous lymphoma cells between these high leukemia AKR/J and AKR/Cu substrains, and reveal that spleen cells from such primed mice generate an H-2 restricted cell-mediated lymphocytic (CML) ' response in vitro when cultured with cells of the appropriate AKR substrain.
This CML response has the following characteristics: 1) priming in vitro and culture with immunogen in vitro are required; 2) sensitization in vivo and restimulation in vitro can be elicited with AKR cells of thymus, spleen, and lymphoma origin; 3) lymphoma and T- and B-cell-enriched, mitogen-stimulated target cell populations are lysed by the effectors; 4) the effector cells are Thy positive; 5) the parameters of the CML response are similar to those reported for the H-Y ( 3) and minor H antigen ( 4) systems.
Using a variety of mouse strains as sources of target cell populations, the data of Table 1 show that 1) the Thy antigen is irrelevant to the CML response, thus AKR/Cu (Thy 1.2) AKR/J (Thy 1.1) effectors lyse CBA and B10.BR, but not C3H cells; 2) B10.BR cells either bear multiple antigens, or a cross-reacting antigens, since they are recognized and lysed by sensitized cells of both AKR substrains; 3) AKR/J and CBA/J cells share the same or similar critical antigen(s) as do AKR/Cu and C3H cells; 4) a non-H-2 antigen(s) is being recognized since lysis of H-2k CBA, C3H, and B10.BR cells occurs, but at least partial homology at the H-2 locus is required, as shown by the failure to lyse B10 cells; and 5) target cell homology at either the D or K end of the H-2 locus is sufficient for lysis by AKR/J effector cells, resulting in lysis of C3H.OH, B10.A, and B10.AKM target cells, whereas homology at the D-end of the H-2 locus is required for lysis by AKR/Cu effector cells, thus no lysis on B10.AKM target cells. Similar results and interpretations are obtained when these strains are used as a source of in vitro immunogens or blocking cells.
This differential H-2 restriction of the CML response could reflect either differential modification of the K- and D-end H-2 molecules by the discrepant AKR/J and AKR/Cu antigen(s), or differential immune responsiveness of these AKR substrains (? non-H-2 IR genes) to modified H-2K and D-end products on cells of the reciprocal substrain.
To summarize, the data indicate that one or more minor histocompatibility antigens distinct from the Thy antigen, prime AKR/J and AKR/Cu mice for a secondary CML response, during the course of rejection of the reciprocal strain's tumor cells. Both T and B cells as well as primary lymphoma cells bear the antigen(s). Although previous studies 1) suggest that the histocompatibility antigen(s) is linked to the Thy antigen and 2) find no evidence for genetic disparity at nine other linkage groups including chromosome 17 (H-2), the possibility remains that the antigen(s) is coded by a locus outside of the section of chromosome 9, linkage group II, which is known to differ between these two substrains. Backcross studies will be required to prove or disprove linkage to the Thy antigen and chromosome 9.
1. Acton, R.T., Blankenhorn, T.C., Douglas, T.C., Owen, R.D., Hilgers, J., Hoffman, H.A., and Boyse, E.A. (1973).
Nature New Biol. 245: 8.
See also MGI.
2. Zatz, M.M. (1978). Cell. Immunol. 36: 251.
See also MGI.
3. Gordon, R.D., Simpson, E., and Samuelson, L.E. (1975). J. Exp. Med. 142: 1108.
See also MGI.
4. Bevan, M.J. (1975). J. Exp. Med. 142: 1349.
See also PubMed.