Siewert, K. | bioRxiv Science

bioRxiv2026

Identification of targetable epitope surfaces from the high resolution structure of the superantigen Staphylococcal Enterotoxin L

Emetic exotoxins secreted by Staphylococcus species (Staphylococcal enterotoxins, SEs) are a major cause of food poisoning cases worldwide and many are additionally classified as superantigens - able to potently activate T cells in an antigen independent manner. Fewer than half of the gene products of the known SE genes have been extensively characterized. The gene for Staphylococcal enterotoxin L (SEL) occurs in both foodborne and clinical isolates but no detailed structural characterization has yet been available. We report here the crystal structure of SEL and confirm its function as a superantigen via direct T cell activation assays. By comparison of the SEL sequence with that of its four closest homologues (SEI, SEK, SEM and SEQ), we have identified binding epitopes unique for SEL and mapped these regions onto the structure. These data provide the first high resolution view of SEL and the basis for the development of diagnostic procedures for its specific detection.

molecular biology↗

bioRxiv2020

Mobilization of tissue-resident memory CD4+ T lymphocytes and their contribution to a systemic secondary immune reaction

While it is generally accepted that tissue-resident memory T lymphocytes protect host tissues from secondary immune challenges, it is unclear whether, and if so, how they contribute to systemic secondary immune responses. Here we show that in human individuals with an established immune memory to measles, mumps and rubella viruses, when challenged with the measles-mumps-rubella (MMR) vaccine again, tissue-resident memory CD4+ T cells are mobilized into the blood within 16 to 48 hours after vaccination. These cells then leave the blood again, and apparently contribute to the systemic secondary immune reaction, as is evident from the representation of mobilized T cell receptor V{beta} clonotypes among newly generated circulating memory T lymphocytes, from day 7 onwards. Mobilization of the tissue-resident memory T cells is cognate, in that memory T lymphocytes recognizing other antigens, e.g. tetanus toxin, are not mobilized, unless they cross-react with the vaccine. These data originally demonstrate the essential contribution of tissue-resident memory T cells to secondary systemic immune responses, confirming that immunological memories to systemic pathogens are maintained (also) by tissue-resident memory T cells. In practical terms, the present work defines day 1 to 2 after antigenic challenge as a time window to assess the entire immunological T cell memory for a certain pathogen, including mobilized tissue-resident memory T cells, and its correlates of effectivity. Capsule summaryThe study demonstrates the rapid and cognate mobilization of tissue-resident memory CD4+ T cells into the blood upon antigenic rechallenge, and their contribution to secondary systemic immune responses.

immunology↗