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The role of MHC class II antigens was investigated in the process of antigen binding by T8+ cells and monocytes (Mo) and in the functions of helper factor (HF) and suppressor factor (SF). Monoclonal antibodies (MoAbs) to HLA-DR, DC and SB determinants were used in immunofluorescence, inhibition of antigen binding and affinity chromatography of HF and SF. Indirect immunofluorescence studies suggest that T lymphocytes from peripheral blood of healthy subjects have a small proportion of cells expressing HLA-DR, β chain determinants (1.4-3.8%). These belong predominantly to the T8+ subset olcells (4.6-8.%), with only a very small proportion in the T4+ cells (0.1-1.8%) However, DC1 on DRw6+ T cells and SB2,3 on any HLA typed cells were found in significantly greater proportion than the DR antigens in both T8+ and T4+ cells, though this was again greater on T8+ (30 and 25%) than T4+ (8.3 and 14.4%) cells. Although Mo had a greatly increased proportion of cells with DR-β chain determinants (27-45%) than the T8+ cells, the converse was found with DC1 and SB2,3 determinants (13.9 and 11.4%). Inhibition of 125I-streptococcal antigen (SA) binding to T8+ cells and to Mo by MoAbs to the class II antigens showed that DR-β chain monomorphic or polymorphic antibodies and DC 1 antibodies inhibited binding to both cell types by 66-94%. However, MoAbs to IDR-α chains or to the SB2,3 determinant failed to yield significant inhibition. Affinity chromatography studies of HF and SF revealed that the DR-β chain monomorphic and DC1 antibodies bound HF and SF activities and that this was not found with the DR-β chain polymorphic or SB2,3 antibodies. The results of inhibition of 125I-SA binding to T8+ cells and Mo, and absorption of HF and SF by affinity chromatography with MoAbs suggest four categories of recognition of human MHC class II antigenic determinants. (1) Class II determinants shared by the T8+ cells, Mo, HF and SF and recognized by MoAbs to monomorphic β chains (DA6.231) and to DC1. (2) Class II determinants shared only by the SA binding T8+ cells and Mo and recognized by the MoAbs to a polymorphic β chain (DA6. 164) and to a monomorphic DR determinant (OK.Ial). (3) Class H determinants shared only by the HF and SF and recognized by the MoAbs to one of the α chains (TAL.1B5). (4) Class II determinants not detected on the two cells or the two T cell factors. [ABSTRACT FROM AUTHOR]

Binding of streptococcal antigen was compared between T8+ cells and monocytes (Mo) from DRw6+ and DRw6- subjects. Both T8+ cells and Mo from DRw6- subjects bind streptococcal antigen (SA) specifically and almost entirely at a concentration of 1000 ng per 0.1 ml. However, the DRw6+, T8+ cells bind SA at a concentration of 1 ng but the DRw6+ Mo bind SA at both 1 and 1000 ng of SA per 0.1 ml. The HLA-DR-dependent shift in the binding concentration of SA applied to Mo as well as T8+ cells, except that the DRw6+ Mo showed a biphasic response (1 and 1000 ng) of SA binding. Comparative inhibition studies revealed that the antigen binding T8+ cells, unlike Mo, are inhibited with monoclonal anti-T8 and -T5 antibodies and anti-suppressor factor antiserum. Neither cell was inhibited by anti-T4, M1, F(ab), IgG, IgM, VH null cell or helper factor antibodies, and anti-T3 antibodies showed variable inhibition of SA binding to T8+ cells but no inhibition to Mo. A functional comparison was carried out between the antigen binding cells and helper and suppressor activities in unseparated mononuclear cells. T4-depleted and T8-depleted populations of cells. The concentration of SA binding to the T8+ cells was the same as that required to elicit helper activity but reciprocal to the broad range of SA concentrations necessary to induce suppressor cell activity. The results are interpreted on the basis of the hypothesis that the antigen binding T8+ cell functions as a contrasuppressor cell which prevents the major subset of the T8+ cells inhibiting the T4+ cells. [ABSTRACT FROM AUTHOR]

T cells from the spleens of C57BL 10 (H-2b) mice 7–12 days after immunization with P815Y (H-2d) mastocytoma cells have been shown to co-operate synergistically with an adherent component of non-immune starch induced peritoneal cells in the cytostasis of target cells. Although significant values for synergy could be obtained using the (125I) UdR incorporation assay to measure cytostasis, normal peritoneal cells were incapable of co-operating with T cells in cytolysis as measured by 51Cr release from pre-labelled target cells. Initially, the synergistic interaction was immunologically specific, but non-specific activity could be induced by challenge with specific antigen. [ABSTRACT FROM AUTHOR]

The antigen binding capacity and function of T cells which adhere to the lectin Vicia villosa (VV) or to streptococcal antigen (SA) have been studied. VV-adherent T8+ cells (T8+ VV+) bind 125I-SA whereas VV non-adherent T8+ cells (T8+ VV-) bind little SA. Similarly, SA-adherent T8+ cells (T8+ SA+) bind 125I-SA specifically, whereas SA-non-adherent T8+ cells (T8+ SA-) show little binding of 125I-SA. The SA binding T8+ VV+ or T8+ SA+ cells can present the antigen to T4+ helper cells which generate helper factors and these enhance anti-DNP-antibodies, when incubated with mouse spleen cells and DNP-SA. Parallel reconstitution studies with either T8+ VV- or T8+ SA- cells have revealed that both subpopulations of cells can suppress T4+- helper cell activity. Further reconstitution experiments between the T8+ VV- (or T8+ SA-) antigen presenting cells and T8+ VV- (or T8+ SA-) suppressor cells suggest that the former can also prevent the latter cells from inhibiting T4 helper cells, so as to function as contrasuppressor cells. Cross-over, reconstitution studies between the VV and SA separated cells have confirmed that the T8+ VV+ and T8+ SA+ cells have similar functions, in SA binding, presenting and contrasuppressor activities. The dose-response curve of binding 125I-SA to T8+ cells is dependent on the HLA-DR type of cells and the binding of 125I-tetanus toxoid was similar to that of 125I-SA. Whereas DRw6- T cells bind predominantly 1,000 ng SA or tetanus toxoid, DRw6+ T cells bind 1 ng and lo a lesser extent 1,000 ng of either antigen, HLA-DRw6+ subjects can be considered as high responders for their T cells bind optimally at low concentrations of antigens which induce helper and contrasuppressor functions. In contrast, HLA-DRw6- subjects can be considered as low responders, as their T cells bind optimally at high concentrations of antigens and only the latter induce helper and contrasuppressor functions. [ABSTRACT FROM AUTHOR]

Regulation of the human immune response was studied by sequential separation of subsets of T cells, followed by assessment of their helper and suppressor functions in a series of reconstitution experiments. T8+ lymphocytes were separated by panning on streptococcal antigen (SA) coated plates into T8+ SA-adherent cells (T8+SA+) and T8+ SA-non-adherent cells (T8+ SA- ). The helper and suppressor functions of the T8 +SA+ and T8+SA+ cells, reconstituted with T4+ helper cells were then studied by a direct antibody forming cell assay. T4+ cells will not induce helper activity by 1000 ng SA alone but require the accessory function of monocytes (Mo). However, replacing Mo by T8+ SA+ cells will elicit a similar helper activity by T4+ cells and SA as that induced by Mo. In addition to the antigen-specific presentation and induction of helper activity, the T+ SA+ subset displays the properties of antigen-specific contrasuppressor cells. Thus, reconstitution of T4+ cells and T8+ SA+ (suppressor cells) with T8+ SA+ and 1000 ng SA induces helper and no suppressor activity. Substitution of Mo for the T8+SA+ cells converts the helper lo a predominantly suppressor-cell function. T8+ SA- cells elicit suppression with 1 ng SA in the absence of accessory cells and reconstitution with Mo, T8+ SA+ or T4+ cells failed to affect the suppressor activity. Total reconstitution of the four principle subsets of T4+ T8+ SA+,T8+ SA+ cells and Mo elicited similar antigen dose-dependent responses as those of the unseparated mononuclear cells. It seems that all four cell subsets are required for optimal immunoregulation. We suggest that the T8+ SA+ can present antigen to T4+ helper cells and induce helper activity, but in addition these cells can prevent the suppressor subset of T8+ cells from inhibiting T4+ helper cells and function as contrasuppressor cells. The mechanism of these functions is not known but HLA class II antigens might play an essential role in antigen binding, presentation and contrasuppression of the T8+ SA+ cells, as the latter are significantly enriched in Ia+ cells. [ABSTRACT FROM AUTHOR]