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

S Sarma, XF Bai, J Liu, KF May Jr, P Zheng, Y Liu - Cancer research, 2003 - AACR
S Sarma, XF Bai, J Liu, KF May Jr, P Zheng, Y Liu
Cancer research, 2003AACR
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 …
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.
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