The strongest primary cytotoxic responses in all species are induced by allogeneic histocompatibility antigens. This finding, which is associated with a relatively high frequency of alloreactive precursor cells (1-10%) (1, 2), has been difficult to understand within the context of the host's autologous immunological environment, including the demonstration of major histocompatibility complex (MHC)a-restricted cytotoxicity (3, 4). It has recently been reported that alloantigen-stimulated cytotoxic lymphocytes lyse autologous cells treated with trinitrobenzene sulfonic acid (TNBS) (5). These results have raised the possibility that alloantigens can resemble self determinants that are associated with certain foreign (X) antigens (5). Thus, cytotoxic T lymphocytes (CTL) directed against alloantigens may be a manifestation of the host's ability to respond to one or more self plus X antigens. If such a proposal were correct, two important questions to be addressed to further analyze this hypothesis are: (a) whether alloantigen-activated CTL can lyse self targets recognized in association with haptenic or viral determinants other than trinitrophenyl (TNP), and, if so, whether distinct populations of allo-induced CTL can distinguish between self plus TNP and self plus X target cells; and (b) can potent effector cell activity induced against non-H-2 antigens recognize self target cells modified with TNP? Our results indicate that alloantigen-activated CTL can lyse autologous, fluorescein isothiocyanate (FITC)-conjugated target cells, and, in addition, that distinct clones of these effector cells lyse self plus TNP and self plus FITC target cells. The present results also illustrate that, in contrast to these hapten-self targets, male target cells expressing the H-Y antigen are not lysed by such allogeneic effector cells. Furthermore, the present study demonstrates that anti-H-Y CTL populations with quantitatively equal or greater activity than alloantigen-activated effector cell populations do not lyse self targets modified with TNP. These findings are discussed in the context of the self and X antigenic determinants involved in allogeneic and self-restricted CTL models.
Materials and Methods
AmmalsThe C3H/HeN and DBA/2 strains were obtained from the Animal Production Facility, National Cancer Institute, Bethesda, Md. All B10 eongenic mice were purchased from The Jackson Laboratory, Bar Harbor, Maine i Abbrevtattons used m thzs paper. ACK, ammonium chlorlde-lysmg solution; BSS, balanced salt solution, Con A, concanavalin A; CTL, cytotoxic T lymphocyte(s); FITC, fluorcscein isothiocyanate; MHC, major histocompatibility complex; TNBS, trinitrobenzene sulfonic acid, TNP, trinitrophenyl, X, foreign.