Tumor Antigens as Inappropriately Expressed Normal Alloantigens

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Abstract
Preliminary tests of three BALB/c myeloma tumors for ability to elicit immune responses in BALB/c mice showed that the only highly immunogenic one was MOPC-167. BALB/c mice immunized with this tumor developed cytotoxic T lymphocytes (CTLs) that lysed MOPC-167 cells specifically. When challenged with 5 × 105 MOPC-167 cells (about 1000 times the LD50 dose) labeled with 131I-iododeoxyuridine, tumors failed to develop in immunized animals and whole-body counts showed that the labeled MOPC-167 cells were rapidly eliminated. The cross-reactions of these CTL were unusual: they caused essentially no lysis of eight other BALB/c tumors, including three myeloma tumors, but they lysed extensively six out of nine tumors of DBA/2 mice (a seventh was lysed weakly). In contrast, the CTL elicited by MOPC-167 in (BALB/c × DBA/2)F1 hybrids did not lyse P815, the most sensitive of the DBA/2 tumors, and had less lytic activity against MOPC-167. CTL elicited by MOPC-167 in other BALB/c hybrids (BALB/c × NZB and BALB/c × C57BL/6) had the same reactions and cross-reactions as those elicited in purebred BALB/c mice. All of these observations suggest that MOPC-167 expresses an alloantigen that normally is absent in BALB/c mice but present in DBA/2 mice and in many DBA/2 tumors. The possibility that CTL elicited by immunization with a syngeneic tumor might be directed to inappropriately expressed alloantigens on the tumor cells was supported by observations with L5178Y: this lymphoma was one of the DBA/2 tumors not lysed by BALB/c anti-MOPC-167 CTL, but it was lysed by the CTL elicited in DBA/2 mice with MOPC-167 or with normal BALB/c spleen cells. Hence L5178Y, although of DBA/2 origin, appears to express antigens that are the same or strongly cross-reactive with an alloantigen that is absent in DBA/2 mice and present on normal BALB/c spleen cells and on a BALB/c myeloma tumor (MOPC-167).