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Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.

For a series of immunological diseases including asthma, inflammatory arthritis and experimental allergic encephalomyelitis the non-classical major histocompatibility complex (MHC) genetics of man and mouse has been making rapid progress. Information is available not only for the disease associations of individual candidate genes but also from the first genome scans. In both species the proinflammatory cytokine genes and/or their related receptors and inhibitors (IL-1, IL-1r, IL-1ra, IL-2, IL-6r, TNF-alpha), and to a lesser extent the anti-inflammatory cytokine IL-4 are implicated as candidate control elements. In contrast, genes for the signalling and adhesion CD molecules have so far been inconspicuous. Most of the polymorphisms so far detected have been in the regulatory sequences of these genes, rather than in the exons. It is suggested that the benefit conferred on an individual by greater flexibility in its immunoregulatory machinery may be responsible for maintaining this form of polymorphism.

In this study we investigate the 57 kD heat shock protein of Chlamydia trachomatis for potential HLA-B27 restricted T cell epitopes. This protein is known to elicit T cell immunity, as judged by delayed type hypersensitivity. We synthesized 24 peptides containing the B27 anchor amino acid arginine at position 2, according to the rules previously described for peptide binding to MHC class I molecules. The nonamer peptides were tested in an in vitro assembly assay; six out of the 24 peptides bind to HLA-B27 although their sequences only partially match the HLA-B27 binding motif. Two of these six peptides carry negatively charged amino acids which apparently fit into the P1 pocket and in three out of the six a positively charged amino acid fits into the P3 pocket. In addition, two octamer peptides stabilized the HLA-B27 molecule without containing an appropriate amino or carboxy terminus. Therefore our data suggest that current binding rules will need to be refined before they can be used to accurately predict potential T cell epitopes. Furthermore our HLA-B27-binding peptides should prove useful probes for the study of the processing and presentation of this bacterial antigen, and of changes in the T cell repertoire induced by this form of infection.