E Kushnir

Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell-stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation.

Mice expressing the minor lymphocyte stimulation antigens, Mls-1a, -2a, or -3a, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V beta 3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor V beta element.

Fetal thymus organ culture was used to study the expression and function of antigen-specific, major histocompatibility complex-restricted receptors on thymocytes. Receptor gene rearrangement and expression occurred de novo in organ culture indicating that these events are induced in the thymus itself, presumably in response to thymus-derived stimuli. During organ culture a population of immature thymocytes expressing low levels of receptors developed first, and then diminished as mature thymocytes with high levels of receptor expression appeared. Continuous culture with antireceptor antibody modulated receptor from the surfaces of immature thymocytes, but did not prevent their appearance or accumulation. By contrast, appearance of receptor-bearing mature thymocytes was prevented in the presence of antireceptor antibody. These results indicate that the receptor is not essential for the generation of immature thymocytes but is involved in the selection or maintenance of mature cells from this pool.