Tumor-Associated Transplantation Antigen Distinct From H-2k-like Antigens on a BALB/c (H-2d) Fibrosarcoma2

Abstract

To ascertain whether the foreign H-2.1, H-2.5, H-2.11, H-2.23, and H-2.25 antigens on a 3-methylcholanthrene-induced BALB/cLacDp (C) (H-2^d) fibrosarcoma C-1 may represent the fibrosarcoma's Individual tumor-associated transplantation antigen (TATA), in vivo Immunogenicity tests were performed in C mice (H-2^d); In (BALB/cLacDp × C3Hf/HeDp)F₁ (CC3F₁), (BALB/cLacDp × AKR/RdDp)F₁ (CAKF₁), and (BALB/cLacDp × B10.BR/SgSn)F₁ (CBRF₁) mice (all H-2^d × H-2^k); In (BALB/cLacDp ×A/HeN)F₁ (CAF₁) mice (H-2^d × H-2Q); In (BALB/cLacDp ×DBA/2ChR)F₁ (CD2F₁) mice (H-2^d ×H-2^d); in (BALB/cLacDp × C57BL/6JDp)F₁ (CB6F₁) mice (H-2^d ×H-2"); and In (BALB/cLacDp × N:NIH/Dp)F₁ (CNIHF₁) mice (H-2^d × H-2^q). The C-1 tumor lost its Immunogenlclty only In CC3F₁ mice and partially in CAF₁ mice. Multiple immunizations with C-1 cells in C and hybrid mice showed that C mice developed both In vivo resistance to tumor challenges of 10⁵ C-1 cells (anti-TATA immunity) and production of antibodies to H-2^k antigens as revealed by a complement-dependent cytotoxicity assay on normal C3Hf/HeDp (C3) lymphocytes. No effector lymphocytes to H-2^k antigens were, however, found In the mice that had detectable levels of anti-H-2^k antibodies. CC3F₁ animals were unable to mount both antl-TATA and antl-H-2^k Immune responses, whereas CAKF₁, CBRF₁ and, to a lesser extent, CAF₁ mice displayed antlTATA Immunity In the absence of anti-H-2^k antibody production. CD2F₁ mice behaved like C mice, whereas CB6F₁ and CNIHF₁ crosses were resistant to tumor challenge but had lower titers of anti-H-2^k antibodies than did C mice. A time-course study of ant-H-2^k antibody production in C mice revealed a peak In the production of antibody after the sixth Immunization, with a very low or undetectable level of such antibodies being evident after one or two immunizations, when a clear antitumor Immunity was present. In the last experiment, immunization of C mice with irradiated C-1 cells “coated” with C anti-C3 sera or C anti-C-1 sera inhibited antl-H-2^k antibody production without affecting the anti-TATA Immunity. We conclude that H-2^k antigens and TATA are probably independent antigenic entities on C-1 cells or at least that the largest part of TATA cannot be formed by H-2 allen determlnants.