HLA‐D/DR Restriction of Macrophage‐dependent Antigen Activation of Immune T Lymphocytes: Cross‐reacting Allogeneic HLA‐D/DR May Partly Substitute for Self HLA‐D/DR

Abstract

Optimal proliferative response of T lymphocytes to purified protein derivative of tuberculin (PPD) in vitro requires that antigen be presented by autologous macrophages or allogeneic macrophages sharing HLA-D/DR determinants with the T cell donor. In some cases, however, T cells may respond to a limited extent to PPD in association with macrophages expressing different HLA-D/DR determinants. In this paper experiments are presented where various combinations of T cells and HLA-D/DR disparate macrophages were stimulated with PPD. We often found a stronger PPD-specific response in HLA-D/DR-incompatible combinations in which the macrophages carried HLA-DR antigens known from serological studies to be cross-reactive with those of the T cell donor than in combinations in which this was not the case. Thus, the cross-reactions detected by serology may sometimes be reflected on a functional level in T lymphocyte/macrophage cooperation.

Antigen Presentation by Vascular Endothelial Cells and Epidermal Langerhans Cells: The Role of HLA‐DR

“…HLA-DR ANTISERA In order to further investigate whether the HLA-DR determinants on endothelial cells were involved as restriction elements, we used xeno-anti la-like or hyper-immune polymorphic allo-anti HLA-DR antisera to inhibit antigenpresentation. The ability of anti HLA-DR antisera, reacting with cell surface determinants on M0, to inhibit the T cell antigen response in vitro, has been previously documented (Bergholtz & Thorsby 1980), and was similar to that shown in experimental animals (Thomas et al 1977).…”

“…The fact that completely HLA-DR incompatible endothelial cells were, at high concentrations, capable of reconstituting the T ceil response could be due to a variety of reasons. One is the cross-reactivity of the DR determinants as has previously been shown for T cell M0 interactions (Bergholtz et al 1980). Another possibility might be that EC carry other antigenic determinants which are in linkage disequilibrium to HLA-DR (Mores & Stasney 1976 and that these unique EC antigen molecules might also represent a putative restriction element.…”

HLA‐D Region Molecules Restrict Proliferative T Cell Responses to Antigen

“…Thus, the response is self HLA-D restricted. This was first shown in our laboratory for the T cell response to the soluble antigen PPD (purified protein derivative of tuberculin) (Bergholtz & Thorsby 1977) and has later been confirmed and extended by us and others for many different antigens, both after in vivo an in vitro priming (Bergholtz & Thorsby 1978, Hansen et al 1978, Seldin & Rich 1978, Thorsby & Nousiainen 1979, Berle & Thorsby 1980. The proliferating T cells belong to the T4 + /T8-(Th/a) sub-set (Reinherz & Schlossman 1980).…”

“…It is possible that part of the previously described cross-reactivity of anti-DR antibodies is due to contaminating MT antibodies. Even though the data reported above may equally well be explained by cross-reactions between restricting HLA-D/DR determinants (Bergholtz et al 1980), a more straightforward explanation would be restriction by other Class II molecules i.e. MT.…”

“…We have not found any influence of sharing of HLA-ABC molecules between APC and T cells. On the other hand, we recently reported that a stronger antigen-specific response was often seen in completely D/DR disparate combinations if the D/DR determinants of the T and APC donors belonged to the same serologically cross-reacting group (Bergholtz et al 1980). Thus, the serological cross-reactions between DR specificities seemed to be refiected on a functional level in T/APC cooperation.…”