Lung tumor-associated derepressed alloantigen coded for by the K region of the H-2 major histocompatibility complex

Abstract

Transplacental induction of lung tumors in C3HfeB/HeN (C3Hf) strain mice can be readily achieved with the carcinogen 1-ethyl-1-nitrosourea. Several of these tumors express, as a tumor-associated transplantation antigen (TATA), a normal tissue alloantigen present in strain A and C3H/HeN (C3H) mice. In the present study it was shown that the tumor-associated alloantigen on the C3Hf-derived lung tumor 85 was present in all mice of H-2(a) and H-2(k) haplotypes tested and in CBA (532) strain mice (H-2(ka) haplotype). Studies using congenic-resistant and recombinant strains of mice indicated that the genetic locus controlling the expression of this antigen was either within or to the left of the H-2K region of the major histocompatibility complex (MHC). Thus the antigen was expressed in B10.A (4R) mice (kkbbbb MHC haplotype) but not in B10 (bbbbbb) or B10.AQR mice (qkkddd). The antigen was expressed in all tissues tested of C3H and A strain mice. It was not detected on any tissue tested including embryo tissue of C3Hf mice or mice of MHC haplotype other than H-2(k) or H-2(a). Because C3Hf strain mice were originally derived from C3H strain mice (H-2(k)), the MHC haplotype of C3Hf mice has been provisionally designated H-2(kb). The finding of a tumor-associated change in the expression of a H-2K region-coded antigen is consistent with the concept that MHC-coded antigens may act as targets for immunological surveillance of tumors.

Role of the Major Histocompatibility Complex Class I Antigens in Tumor Growth and Metastasis

“…For example, the C3Hf-derived lung carcinoma line (L T-85) is rapidly rejected upon transplantation into parental C3Hfmice (100). Since these class I genes contain unique restriction fragments not detectable in the genome of the mouse strains from which the respective tumors were derived, they must have been generated by multiple recombination events among endogenous class I genes and must have occurred during the course of tumorigenesis.…”

Separation of the tumor‐associated transplantation antigen (TATA) from the alien H‐2k antigens expressed on a methylcholanthrene‐induced tumor

“…Moreover, the TATA of a chemically induced murine lung tumor has been mapped to the histocompatibility locus although it is not certain whether it is actually an H-2 molecule (Gipson et al, 1978). Related to these findings is the observation that certain public specificities which are not complement-dependent cytotoxic targets on normal tissue can become cytotoxic targets on tumor cells Robinson et a f .…”

“…These results notwithstanding, it can be demonstrated serologically that some murine tumors do express alien histocompatibility antigens (Meschini et af., 1977;Garrido et al, 1976) and, in some cases, that these antigens can function as targets for an immune response (Festenstein et al, 1977;Roman and Bonavida, 1979). Moreover, the TATA of a chemically induced murine lung tumor has been mapped to the histocompatibility locus although it is not certain whether it is actually an H-2 molecule (Gipson et al, 1978). Related to these findings is the observation that certain public specificities which are not complement-dependent cytotoxic targets on normal tissue can become cytotoxic targets on tumor cells Robinson et a f .…”

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

“…Furthermore, the expression of MHC antigens in many malignant tumors has been found to be different from that in normal cells (2)(3)(4)(5). The differences vary from quantitative change to qualitative modification, as exemplified in several tumor cells that expressed attenuated structures of alien specificities distinct from those of their normal counterparts (6,7). These alterations could be caused by mutation, recombination, or activation of normal MHC genes (8,9).…”