HLA‐D Restriction of the Macrophage‐Dependent Response of Immune Human T Lymphocytes to PPD in Vitro: Inhibition by Anti‐HLA‐DR Antisera

Abstract

The response of T cells from sensitized individuals to low doses of PPD in vitro is macrophage-dependent. By testing different allogeneic combinations of macrophages and T lymphocytes, it was found that an optimal response required that antigen be presented by macrophages sharing at least one of the HLA-D determinants of the T cell donor. Antisera recognizing HLA-A, -B or -DR antigens were found to be able to inhibit this proliferative response. The anti-HLA-DR antisera were found to exert their inhibitory effect only when directed towards an antigen shared by the donors of the T lymphocytes and the macrophages. Anti-HLA-A and -B sera, however, had an inhibitory effect when reactive with the responding T lymphocytes, irrespective of their reactivity with the cooperating macrophages. It is concluded that an optimal secondary response of in-vivo-immunized T lymphocytes to PPD requires the combined recognition of the antigen and 'self' membrane structures encoded by the HLA-D locus.

Recognition of Hapten-Modified Cells In Vitro by Human T Lymphocytes

“…In the human, HLA-A-or -B-locus homology requirements between killer and target cells have been reported for cytotoxic responses generated against the Y male antigen (13), influenza-infected cells (14,15), and hapten-modified cells (16,17). In contrast, we and others have reported the importance of HLA-D-region determinants in the generation of human proliferative responses to haptens and other conventional antigens (18)(19)(20)(39)(40)(41). In this study we have found that antigen presentation requirements for induction of cells capable of cytotoxic effector function also differ from those for proliferative responses.…”

“…Available data suggest that the proliferative responses in vitro are related in magnitude and specificity to delayed hypersensitivity reactions (49)(50)(51). Investigations of both proliferative responses to hapten-conjugated cells (18)(19)(20) and to purified protein derivative (39)(40)(41) suggest that the autologous determinants involved in delayed hypersensitivity reactions are encoded in the HLA-D region. Haptenic determinants on soluble proteins or membrane fragments (52) …”

Specific binding of antigen onto human T lymphocytes.

“…It is a somewhat unexpected finding that free mannan alone could specifically bind T lymphocyte membranes because it has previously been demonstrated that the T cell receptor is specific for antigen associated with a MHC product (8)(9)(10)(11)(12). Such an association is indeed required for mannan inasmuch as monocyte-T lymphocyte interactions in mannan-induced T cell responses are HLA class II-restricted (32 (29).…”

“…Research performed on murine or human models has suggested direct binding of antigen alone onto primed T cells (1)(2)(3)(4)(5)(6)(7). However, most reports have shown that T lymphocytes recognize the antigen in association with a major histocompatibility complex (MHC)' product, and not alone (8)(9)(10)(11)(12).…”

Antigen-induced monocyte procoagulant activity. Requirement for antigen presentation and histocompatibility leukocyte antigen-DR molecules.

“…In preliminary experiments with purified populations of monocytes and lymphocytes, we have found the monocyte to be the site ofinhibition ofthe procoagulant response by this monoclonal anti-HLA-DR antibody. The use of [3H]thymidine uptake by immune T cells has shown that the antigen presentation step is interfered with by anti-HLA-DR antisera (36). We have recently described a PPD reactive human T cell clone that mediates the procoagulant response to PPD presented by autologous monocytes (39).…”