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Original H-2d and alien H-2k-like antigens of a BALB/c fibrosarcoma as defined by in vitro and in vivo studies of cell-mediated immunity

✍ Scribed by Marialuisa Sensi; Giusi Carbone; Giorgio Parmiani


Publisher
John Wiley and Sons
Year
1980
Tongue
English
Weight
805 KB
Volume
10
Category
Article
ISSN
0014-2980

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✦ Synopsis


Abstract

The present study examines the immunosensitivity and the immunogenicity of both original H‐2^d^ and alien H‐2^k^‐like antigens of the BALB/c (H‐2^d^) fibrosarcoma C‐1 as detected by in vitro and in vivo cell‐mediated cytotoxicity (CMC) assays. It was found that ^51^Cr‐labeled C‐1 cells were lysed in vitro by C 57 BL/6 anti‐H‐2^d^ lymphocytes. The specificity of this reaction was shown by cold inhibition experiments in which the anti‐H‐2^d^ cytotoxic activity on YC8 (H‐2^d^) targets was inhibited by unlabeled YC8 or C‐1 but not by C3UR11 (H‐2^k^) tumor cells. Both D^d^‐ and K^d^‐encoded antigens were recognized by appropriate cytotoxic effectors. The immunogenicity of H‐2^d^ antigens of C‐1 was revealed by the ability of C 57 BL/6 anti‐C‐1 lymphocytes to lyse YC8 targets. The expression of H‐2^k^‐like alien alloantigens on C‐1 was indicated by the finding that anti‐H‐2^k^ cytotoxic T lymphocytes (CTL), generated by culturing BALB/c spleen cells immune to BALB.K (H‐2^k^), C3Hf (H‐2^k^) or A (H‐2^a^ = H‐2^k/d^) tissues with the cells of the same strain used for immunization, lysed C‐1 targets. The cytotoxicity of these anti‐H‐2^k^ CTL against C 3 UR11 (H‐2^k^) targets could be specifically inhibited by cold C 3 UR 11 or C‐1 cells but not by two other BALB/c tumors. Using recombinant H‐2‐congenic mice, it was shown that both D^k^ and K^k^ antigens were recognized by CTL on C‐1 cells. The immunogenicity of the H‐2^k^‐like antigens, however, could not be detected in vitro. In fact, effector spleen cells from BALB/c mice immune to C‐1 did not develop any detectable cytotoxicity against C 3 UR 11 targets as assayed either by a direct in vitro test or after in vitro restimulation with C‐1 sarcoma cells. A similar experimental design was adopted in Winn assays carried out by mixing spleen cells of BALB/c immune mice with either C‐1 or C3 UR 11 targets and injecting the mixtures in BALB/c or hybrid recipients. These in vivo tests revealed the presence of both H‐2^d^ (K^d^ and D^d^) and H‐2^k^‐like (K^k^ and D^k^) antigens on C‐1. At variance with the in vitro CMC assays, however, the Winn assay also detected the immunogenicity of the H‐2^k^ alien antigens, since BALB/c anti‐C‐1 spleen cells were able to significantly reduce the growth of C 3 UR 11 lymphoma cells in (BALB/c × C 3 Hf)F~1~ hosts.