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The kinetics of iodinated human serum albumin ([125I]Hu-SA) and alpha-fetoprotein ([125I]Hu-AFP) binding and endocytosis by resting and phytohemagglutinin (PHA)-activated human T lymphocytes were studied comparatively. The binding of both SA and AFP appeared considerably increased upon blastic transformation. SA, like AFP, binds in a saturable way to the surface of PHA-stimulated human T lymphocytes at 4 degrees C and is endocytosed at 37 degrees C. Two saturation plateaus were observed by incubating at 4 degrees C activated T lymphocytes with [125I]Hu-AFP at different concentrations (10 ng-250 micrograms/ml), while only one saturation plateau was obtained by incubating cells with [125I]Hu-SA in the same conditions. Scatchard analysis of binding data revealed two types of binding sites for Hu-AFP and one for Hu-SA. Competition experiments using proteins of human and bovine origin are in favor of the presence on the surface of these cells of a common binding site for AFP and SA. Pulse-chase experiments showed that internalized [125I]SA was released mainly in a degraded form from the cells, in agreement with detection by ultrastructural cytochemistry of peroxidase-conjugated SA in lysosome-like bodies by ultrastructural cytochemistry. This contrasts with the intracellular pathway of AFP, which as previously described (Geuskens, M., et al., Eur. J. Cell Biol. 50, 418-427 (1989)), moves to tubular-vesicular structures in the Golgi region and is recycled for the most part undegraded.

Psoriasis can be triggered by haemolytic streptococcal infections. As M protein is a major pathogenic surface antigen in these streptococci, the cross-reactivity between streptococcal M protein surface antigens and human epidermis was investigated. The conserved component common to the few M proteins investigated consists of an alpha-helical 'coiled-coil' configuration, similar to sub-units of human keratin. The amino acid sequence of protein M6, one of the M proteins that has been fully sequenced, was compared with that of 4721 ubiquitous peptides, by computer-assisted analysis using a protein-sequence data bank. Of all human proteins in the data bank 50-kDa keratin type 1 showed the closest homology with protein M6. Further evaluation revealed that this homology mainly involved the heptapeptide repeat patterns, which form the alpha-helical 'coiled-coil' structure, in both M6 and 50-kDa keratin. Cryostat sections of normal, involved and uninvolved psoriatic skin were studied for cross-reactivity with rabbit antisera raised against 10 different M proteins. All these antisera reacted with the stratum corneum of normal and psoriatic epidermis to a variable extent. Staining of keratinocyte cytoplasm was also observed, but this tended to be more prominent in lesional than in uninvolved and normal skin. Some of the M antisera also stained dendritic cells in the upper dermis as well as endothelium and smooth muscle. These cross-reactivities might be relevant to the pathogenesis of post-streptococcal psoriasis.

HLA class II antigens were identified in a group of 44 patients with rheumatoid arthritis (RA) originating largely from the north or northeast of the Indian subcontinent and resident now in east London. Compared with 67 locally typed east London Asian controls, the prevalence of three HLA-DR antigens was raised in the patients: DR1 18.2% v 6.0% chi 2 = 3.99, DR4 20.5% v 11.9% chi 2 = 1.48, and DRw10 27.3% v 8.9% chi 2 = 6.56. These differences were also found when the patients with RA were compared with a larger control group of 110 northern Indians: DR1 18.2% v 7.2% chi 2 = 4.02, DR4 20.5% v 7.2% chi 2 = 5.56, and DRw10 27.3% v 8.1% chi 2 = 9.7. Twenty five (57%) of the patients expressed at least one of these antigens. All patients were also characterised for HLA-Dw types by mixed lymphocyte culture typing. The prevalence of the HLA-DR4 associated Dw types in the patients was: Dw4 2.3%, Dw10 0%, Dw14 11.4%, and Dw15 6.8%. The DR beta 1 chains of DR1 and DRw10 together with the Dw types of DR4 other than Dw10 share amino acid residues in a region of the third hypervariable region considered to be critical in antigen presentation. It is concluded that RA in Indians is associated with these HLA antigens, and data from this study support the hypothesis of a cross reactive epitope common to HLA specificities associated with RA.

Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE.