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Cross-reactivity between streptococcal M surface antigen and human skin
J McFadden1, H Valdimarsson, L Fry
1Department of Dermatology, St Mary's Hospital, London, U.K.
Abstract:
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.
Insights
Streptococcal M protein shares structural similarities with human keratin, potentially explaining how infections trigger psoriasis. This cross-reactivity suggests a link between M protein and skin components in disease development.
Area of Science:
- Immunodermatology
- Microbial Pathogenesis
- Structural Biology
Background:
- Psoriasis can be initiated by hemolytic streptococcal infections.
- Streptococcal M protein is a key surface antigen involved in pathogenicity.
- Investigating cross-reactivity between M protein and human epidermis is crucial for understanding post-streptococcal psoriasis.
Purpose of the Study:
- To investigate the cross-reactivity between streptococcal M protein and human epidermal components.
- To explore the structural basis for potential molecular mimicry between M protein and keratin.
- To assess the relevance of these cross-reactivities in the pathogenesis of psoriasis.
Main Methods:
- Computer-assisted analysis comparing the amino acid sequence of M protein (M6) with human proteins in a data bank.
- Analysis of conserved alpha-helical 'coiled-coil' configurations in M protein and human keratin.
- Immunohistochemical staining of skin sections using antisera raised against various M proteins.
Main Results:
- Protein M6 showed significant homology with 50-kDa keratin type 1, particularly in heptapeptide repeat patterns forming alpha-helical structures.
- M protein antisera reacted with the stratum corneum of normal and psoriatic epidermis.
- Cytoplasmic staining of keratinocytes was more prominent in lesional psoriatic skin; dendritic cells, endothelium, and smooth muscle also showed reactivity.
Conclusions:
- Structural similarities between streptococcal M protein and human keratin suggest a mechanism for molecular mimicry.
- Observed cross-reactivities between M proteins and skin components may contribute to the pathogenesis of post-streptococcal psoriasis.