PMID- 1588277 OWN - NLM STAT- MEDLINE DCOM- 19920623 LR - 20190508 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 175 IP - 6 DP - 1992 Jun 1 TI - Major histocompatibility complex independent clonal T cell anergy by direct interaction of Staphylococcus aureus enterotoxin B with the T cell antigen receptor. PG - 1493-9 AB - The Staphylococcal enterotoxin superantigens stimulate vigorous responses in T cells bearing certain T cell antigen receptor (TCR) V beta regions. In addition to activation, these superantigens also impart negative signals to T cells resulting in a profound state of unresponsiveness or anergy. The Staphylococcus aureus enterotoxins (SE) B and C2 bind to a closely related site on major histocompatibility complex (MHC) human leukocyte antigen (HLA)-DR1 molecules. Only SEB, however, interacts with the TCR V beta 3 region of HA1.7, a human HLA-DR1 restricted T cell clone specific for influenza haemagglutinin. In competition experiments, we demonstrated that the induction of anergy in HA1.7 by SEB is unaffected by the presence of SEC2. These results suggest that SEB-induced anergy is MHC independent and involves a direct interaction between the TCR and SEB. To resolve definitively whether SEB binds directly to T cells in the absence of MHC class II molecules, the cDNAs encoding the HA1.7 TCR were transfected into an MHC class II-negative human T cell line. The addition of SEB to these transfectants resulted in the downregulation of cell surface TCR expression, an increase in the concentration of intracellular calcium ions, the production of lymphokines, and reduced responsiveness to a subsequent challenge with SEB. We conclude that SEB interacts directly with the TCR in the absence of cointeraction with MHC class II molecules, and that this interaction may induce anergy in HA1.7. FAU - Hewitt, C R AU - Hewitt CR AD - Imperial Cancer Research Fund, London, UK. FAU - Lamb, J R AU - Lamb JR FAU - Hayball, J AU - Hayball J FAU - Hill, M AU - Hill M FAU - Owen, M J AU - Owen MJ FAU - O'Hehir, R E AU - O'Hehir RE LA - eng SI - GENBANK/S40279 SI - GENBANK/S44631 SI - GENBANK/S44632 SI - GENBANK/S44633 SI - GENBANK/S44634 SI - GENBANK/S44635 SI - GENBANK/S44636 SI - GENBANK/S44637 SI - GENBANK/X63455 SI - GENBANK/X63456 GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antisense Elements (Genetics)) RN - 0 (Enterotoxins) RN - 0 (Macromolecular Substances) RN - 0 (Receptors, Antigen, T-Cell) RN - 39424-53-8 (enterotoxin B, staphylococcal) RN - SY7Q814VUP (Calcium) RN - VC2W18DGKR (Thymidine) SB - IM MH - Amino Acid Sequence MH - Antisense Elements (Genetics) MH - Base Sequence MH - Binding Sites MH - Calcium/metabolism MH - Clone Cells MH - DNA Replication MH - Enterotoxins/*pharmacology MH - Humans MH - Kinetics MH - Macromolecular Substances MH - *Major Histocompatibility Complex MH - Molecular Sequence Data MH - Polymerase Chain Reaction MH - Receptors, Antigen, T-Cell/drug effects/genetics/*immunology MH - Staphylococcus aureus/physiology MH - T-Lymphocytes/drug effects/*immunology MH - Thymidine PMC - PMC2119262 EDAT- 1992/06/01 00:00 MHDA- 1992/06/01 00:01 PMCR- 1992/12/01 CRDT- 1992/06/01 00:00 PHST- 1992/06/01 00:00 [pubmed] PHST- 1992/06/01 00:01 [medline] PHST- 1992/06/01 00:00 [entrez] PHST- 1992/12/01 00:00 [pmc-release] AID - 92268797 [pii] AID - 10.1084/jem.175.6.1493 [doi] PST - ppublish SO - J Exp Med. 1992 Jun 1;175(6):1493-9. doi: 10.1084/jem.175.6.1493.