On the role of unmutated antigens in tumor rejection in mice with unperturbed T-cell repertoires

Cancer Res. 2003 Sep 15;63(18):6051-5.

Abstract

We investigate here whether P1A, which was the first CTL-recognized and unmutated tumor antigen to be identified, is a tumor rejection antigen for J558 plasmacytoma in mice with an unperturbed T-cell repertoire. We show that although transgenic mice expressing P1A in the thymus have almost complete deletion of P1A-reactive T cells, they reject the B7-1-transfected J558 at a rate comparable with wild-type mice. Thus, P1A is not a necessary tumor rejection antigen for the J558 tumor cells. On the other hand, if anti-P1A CTL response is sufficient for tumor rejection, tumor cells must lose the antigenic epitope to evade CTL destruction. To test this, we analyze whether tumor cells escaping J558-B7 immune spleen cells harbor mutations in the P1A epitope. We find that although the spleen contained a high proportion of P1A-reactive T cells, the recurrent tumor cells have no mutation in the P1A antigenic epitope and remain susceptible to lysis by P1CTL. Thus, the antigen-bearing tumor cells can evade immune destruction in the presence of a high number of P1A-reactive T cells. Taken together, our results demonstrate that in mice with a normal TCR repertoire, substantial numbers of P1A-reactive T cells are neither necessary nor sufficient for tumor rejection and raise interesting questions regarding the significance of T-cell response against unmutated tumor antigens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Immune Tolerance
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / prevention & control
  • T-Lymphocytes / immunology*
  • Transfection

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • tumor rejection antigen P815A, mouse