On the role of unmutated antigens in tumor rejection in mice with unperturbed T-cell repertoires.
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.
Sarma
Supria
S
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Bai
Xue-Feng
XF
Liu
Jin-qing
JQ
May
Kenneth F
KF
Zheng
Pan
P
Liu
Yang
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; C076546:tumor rejection antigen P815A, mouse