Mixed Lymphocyte Reactivity and Cell‐Mediated Lympholysis to D‐End Differences of the Murine Major Histocompatibility Complex

Abstract

In vitro mixed lymphocyte culture (MLC) responses and the in vitro induction of cell-mediated lympholysis (CML) were studied in congenic strain combinations in which the responding and stimulating strains differed either at the entire major histocompatibility complex (MHC) or only at the D end of the MHC. In contrast to previously reported studies, the relative strengths of stimulation by 'D end only' differences or by whole MHC differences were examined by stimulating identical responding populations with titrated numbers of stimulating cells that differed from the responder either at the D end only or over the entire MHC. When tested in this manner isolated D-end differences were sufficient to generate significant MLC and CML responses in each combination tested. Several 'D end only' differences (the responses of B10.A to B10.A(2R); of B10.A(2R) to B10.A; of B10.D2 to B10.HTG; and of B10.HTG to B10.D2 were several fold less efficient in stimulating MLC and CML responses than were control stimulating cells differing over the whole MHC. In contrast, when the mutant D-end allele da was present on the stimulating cell (the responses of B10.D2 to B10.D2(M504) and of B10 to B10.D2(R106)), stimulation by an isolated D-end difference was comparable to stimulation by broader MHC differences. These findings are discussed in terms of the possible functional complexity of the D region.

Suppression of cell‐mediated lymphocytotoxicity against minor histocompatibility antigens mediated by Lyt‐1+Lyt−2+ T cells of stimulator‐strain origin

“…Before attempting to answer this question, we should point out that the finding of culture-induced suppressor cells is not unique: these cells have been demonstrated by several investigators in a variety of experimental systems [14][15][16][17][18][19][20]. Suppressor cells are also generated in allogeneic [21] and syngeneic mixed lymphocyte reaction [22], and as a result of culturing unimmunized cells with allogeneic effect factor [23].…”

Cellular Requirements for the Induction of Cytotoxic T Cells In vitro

“…(6) Helper T cells activated by H-2I or Mis loci coded antigens are: not an absolute requirement for cytotoxic T cell induction , Nabholz et al 1974, Forman & Klein 1975a, b, Melief et al 1975, Hodes et al 1976). …”

“…Similarly, significant and bidirectional generation of cytotoxic activity has also been observed with congenic and non-congenic strains differing at H-2K or H-2D (Nabholz et al 1974, Wagner et al 1975b, Hodes et al 1976. I While studies with recombinant, congenic and mutant mouse strains have conclusively demonstrated that recognition of la determinants is not a corequisite for induction of cytotoxic T cells, they have not eliminated the possibility of a requirement for recognition of cell surface antigens in addition to target cell antigens.…”

T Cells Lacking Immunoproteasome Subunits MECL-1 and LMP7 Hyperproliferate in Response to Polyclonal Mitogens

“…Proliferative response of T cells in a MLR is dependent on recognition of mismatched MHC molecules expressed on allogeneic stimulator cells (23). We assessed proliferation of immunosubunitdeficient T cells in a MLR by stimulating responder splenocytes (H-2 b ) with mitomycin-treated DBA/1 stimulator splenocytes (H-2 q ).…”