Regulatory mechanisms in cell-mediated immune responses. Role of I-J and I-C determinants in the activation of H-2I and H-2K/D alloantigen-specific suppressor T cells.

Abstract

The role of individual H-2I subregion determinants in the activation of H-2I alloantigen-primed mixed leukocyte response suppressor T cells (MLR Ts), as well as their possible expression on stimulator cells required to trigger primed H-2K- or D-specific MLR Ts, was addressed in these studies. Both genetic and serologic studies demonstrated that MLR Ts potentially primed to alloantigens encoded by the entire H-2I region were triggered to MLR Ts factor production only by stimulator cells bearing the priming I-J and/or I-C, but not I-A or I-E alloantigens. The relevant I-J and I-C determinants were demonstrated on a single antigen-presenting cell population that is used in common by independent I-J-specific and I-C-specific MLR Ts. Unexpectedly, the stimulator cell population necessary to trigger MLR Ts primed to class I H-2K or D alloantigens expressed not only the priming class I determinant, but in addition, I-C alloantigens syngeneic with the MLR Ts haplotype. Stimulator populations bearing the appropriate H-2K or D alloantigen but serologically depleted of I-C+ cells or genetically constructed to display MLR Ts-disparate I-C determinants were ineffective stimulators of class I antigen-primed MLR Ts. Thus these data suggest that as allogeneic determinants, I-J- and I-C-encoded molecules are together the major triggering elements for MLR Ts primed to disparate H-2I region determinants. In addition, self-I-C molecule recognition appears to constitute an important feature of the triggering, and by implication, priming process of H-2 class I antigen-specific Ts cells.

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

“…This gain is shown to be due to increase in the proportion of DNAsynthesizing small and medium lymphocytes and to a 50% increase in the percentage of medium and large lymphocytes in the population . Similar data concerning the large diameter of alioantigen-induced suppressor Tceils have been described elsewhere (Wagner et al 1976, Rich et al 1977. The data indicate that SSTC are in the mitotic cycle, although DNA synthesis is not required for their function as judged by their resistance to MC.…”

“…This result means that, unlike other T-subclasses, SSTC may be activated by each MHC product*. However, such an inference is not in accord with other results: I-J subregion distinctions are required for suppressor generation (Liew 1981), I-A and I-E antigens do not induce suppressors at all and the anti-H-2K/ D reaction is restricted by I-C subregion (Rich 1983). Nevertheless, there exist no less prominent opposite data: the distinction in I-A antigen only (even mutant) is sufficient for T-suppressor induction (Shearer & Levy 1983), the T-suppressors induced by non-H-2 foreign antigens may react either to such antigen associated with syngeneic I-A (Fink et al 1983) or I-E molecules (Baxevanis et al 1982), or to I-A restricted T-helper receptors (Asano & Hodes 1983).…”

“…The evidence described above is not in agreement with the reports of anti-H-2 suppressors, tested by MLR inhibition (Czitrom et al 1980) or by deiayed-type hypersensitivity decrease in vivo (Liew 1981), which are shown to require the difference in I-J subregion for their induction or recognize MHC prodtjcts in association with I-J only. Some other data describe the restrictions of T-suppressor reactivity to MHC products (Rich 1983). On the contrary, SSTC and their receptors (see below) in our system react to any MHC products with no requirement for expression of respective allogeneic or syngeneic I-C and I-J products by antigen-bearing TC.…”

Suppressor T cell growth and differentiation. Identification of a cofactor required for suppressor T cell function and distinct from interleukin 2.

“…In the absence of Ts costimulator, activation to MLR-TsF production fails regardless of stimulator cell concentration, indicating that fixation has impaired an additional and requisite stimulator cell function distinct from surface antigen display. MLR-Ts typically interact with stimulator cells of novel I-C + or I-J+C ÷ phenotypes (54). Whether Ts costimulator directly represents an activity of such a stimulator cell or rather the product of a secondary cell that requires stimulator cell interaction is presently unclear.…”