RECURRENT T-CELL RECEPTOR REARRANGEMENTS IN THE CYTOTOXIC T-LYMPHOCYTE RESPONSE IN-VIVO AGAINST THE P815 MURINE TUMOR

P815 is a murine mastocytoma of DBA/2 origin which, although immunogen ic, rapidly develops as a tumor in immunocompetent syngeneic hosts. In this report, we have studied, by a molecular approach, the in vivo al pha/beta T cell response to P815. Both situations of tumor growth afte r engraftment of naive animals or tumor rejection by preimmunized anim als have been analyzed. The spectrum of T cell receptor beta chain rea rrangements in the tumor-infiltrating lymphocytes was found to be high ly variable among individual tumor-bearing mice. However, two rearrang ements, one using V beta 1 and J beta 1.2 segments and one using the V beta 1 and J beta 2.5 segments, with conserved junctional regions, re producibly emerge in most individuals. These two rearrangements thus c orrespond to ''public'' (recurrent) T cell clones, as opposed to ''pri vate'' ones, which emerge in a seemingly stochastic fashion in immuniz ed animals. Importantly, these public cells are observed in situations of either growth or rejection of the tumor. Quantification provides a clear increase in public T cells in secondary responses, but no obvio us correlation between their level and primary tumor rejection. The V beta 1-J beta 1.2 rearrangement is borne by CTL directed against an an tigen derived from P1A, a nonmutated mouse self protein which is expre ssed in P815 but not in normal mouse tissues except testis. A recurren t, public T cell response can thus be observed to an antigen derived f rom a self protein expressed by a tumor.