Role of self and foreign antigenic determinants in allogeneic and self-restricted cytotoxic T cell recognition.

Abstract

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.

HLA-B7 β-pleated sheet-derived synthetic peptides are immunodominant T-cell epitopes regulating alloresponses

“…As we reported previously, Epstein-Barr virus-transformed cells, tumor cells, and PHA-blast cells expressing B7 were lysed by a single CTL line or clone, indicating that the specificity of the CTLs was peptide-dependent 31 but not peptide-specific. However, allo-MHC-restricted CTLs have been well described and characterized in the literature, 34,35 indicating heterogeneity in the specificity of polyclonal alloreactive CTLs. 36 We further attempted to raise long-term T-cell cultures using autologous PBLs pulsed with a mixture of the B7-derived peptides.…”

Specific Suppressor T‐Cells Immune to Antigens of the H‐2 Complex: Receptors, Clonal Structure, Genetic Restriction and Antigenic Markers

“…When each of the CTL fractions was enriched by elution from the corresponding TC monolayer, the in v/vo-induced "monospecific" CTL directed against K*' or D'^ antigens were found to demonstrate cross-cytotoxicity to TC expressing "irrelevant" H-2 antigen (Brondz et al I979e). The same cross-reactivity (CR) of CTL has been demonstrated when they were induced by both H-2 antigens in MLC (Fisher-Lindahl et al 1975, Peavy & Pierce 1975, Vasques et al 1980) and syngeneic cells modified by hapten (Burakoff et al 1976, Levy et al 1980 or by virus (Finberg et al 1978), as well as when cells of mutant strains of mice were used as TC (Melief et al 1980). The CR CTL reflect the peculiarities of their specificity and can be revealed not only in the crude CTL populations but in a part of their clones (Taswell et al 1980, Guimezanes et al 1982, Plata 1982, as well as in cloned CTL precursors (Teh et al 1978).…”

Sperm priming reveals specific autoreactive lymphocyte clones

“…Some evidence favors the theory that autoreactive and antigen reactive populations are the same or similar and largely separate from allore,active lymphocytes (Hausman et al 198 1 ). However, work in humans (Dattner & Levis 1978, Dattner et al 1979, and cytotoxic recognition in mice (Levy et al 1980) suggests that some overlap may exist between the auto-altered-self repetoire and the alloreactive repetoire. The degree of overlap between the auto-altered-self re-petoire and alloreactive repetoire with certain environmental antigens in selected individuals may be important in the pathogenesis of MHC associatcd diseases.…”