The Staphylococcus aureus Enterotoxin B Superantigen Induces Specific T Cell Receptor Down-regulation by Increasing Its Internalization (*)

Superantigens are able to stimulate T lymphocyte populations expressing T cell antigen receptors (TCR) belonging to particular Vβ families. Moreover, the presence of these superantigens may induce long term unresponsiveness (anergy) of these sensitive cells. Some bacterial toxins are potent superantigens. We have analyzed in vitro the capacity of some Staphylococcus aureus enterotoxin superantigens to modulate T cell antigen receptor expression and the cellular mechanisms involved. Staphylococcus enterotoxin B (SEB) induced rapid down-regulation of surface T cell antigen receptors in Vβ3-expressing T lymphocytes, as assessed by flow cytometry. This phenomenon was a consequence of the direct interaction between the toxin and the TCR since it was observed in the absence of cells expressing major histocompatibility complex class II molecules. The cellular mechanism involved in SEB-induced down-regulation of TCR was further investigated. Immunofluorescence and confocal microscopy experiments showed that toxin B induced intracellular accumulation of TCR·CD3 in endocytic vesicles. Moreover, SEB induced an increase in T cell receptor endocytosis as measured using radiolabeled Fab fragments of an anti-CD3 monoclonal antibody. Taken together, our observations indicate that Staphylococcus enterotoxin B superantigen induced changes in the dynamics of surface T cell receptors, which resulted in the fast reduction of membrane receptor numbers.

[1]  R. Klausner,et al.  Binary and ternary complexes between T-cell receptor, class II MHC and superantigen in vitro , 1994, Nature.

[2]  C. Geisler,et al.  CD3 gamma contains a phosphoserine‐dependent di‐leucine motif involved in down‐regulation of the T cell receptor. , 1994, The EMBO journal.

[3]  Don C. Wiley,et al.  Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen , 1994, Nature.

[4]  D. Mason,et al.  Antigen Receptors on T and B Lymphocytes: Parallels in Organization and Function , 1993, Immunological reviews.

[5]  H. Macdonald,et al.  Exogenous and Endogenous Mouse Mammary Tumor Virus Superantigens , 1993, Immunological reviews.

[6]  P. Marrack,et al.  The Bacterial and Mouse Mammary Tumor Virus Superantigens; Two Different Families of Proteins with the Same Functions , 1993, Immunological reviews.

[7]  G. Schönrich,et al.  Multiple levels of peripheral tolerance. , 1993, Immunology today.

[8]  J. Lamb,et al.  Generation of monoclonal antibodies against a human T cell receptor beta chain expressed in transgenic mice. , 1992, Hybridoma.

[9]  Alimuddin Zumla.  Superantigens, T cells, and microbes. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  R. O’Hehir,et al.  Major histocompatibility complex independent clonal T cell anergy by direct interaction of Staphylococcus aureus enterotoxin B with the T cell antigen receptor , 1992, The Journal of experimental medicine.

[11]  A. Williams,et al.  Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Davis,et al.  Molecular components of T-cell recognition. , 1992, Annual review of immunology.

[13]  C. Janeway.  The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation. , 1992, Annual review of immunology.

[14]  Z. Brahmi,et al.  Receptor modulation and early signal transduction events in cytotoxic T lymphocytes inactivated by sensitive target cells. , 1991, Journal of immunology.

[15]  G. Schönrich,et al.  Down-regulation of T cell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction , 1991, Cell.

[16]  M. Ferrer,et al.  Modulation of interleukin 2 internalization and interleukin 2-dependent cell growth by antireceptor antibodies. , 1991, The Journal of biological chemistry.

[17]  A. McMichael,et al.  Immune recognition of HLA molecules downmodulates CD8 expression on cytotoxic T lymphocytes , 1991, The Journal of experimental medicine.

[18]  J. Lamb,et al.  Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  C. Benoist,et al.  Superantigens interact with MHC class II molecules outside of the antigen groove , 1990, Cell.

[20]  P. Marrack,et al.  HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells , 1990, The Journal of experimental medicine.

[21]  P. Marrack,et al.  The staphylococcal enterotoxins and their relatives. , 1990, Science.

[22]  C. Pontzer,et al.  The I-A beta b region (65-85) is a binding site for the superantigen, staphylococcal enterotoxin A. , 1990, Biochemical and biophysical research communications.

[23]  H. Boehmer,et al.  Developmental biology of T cells in T cell-receptor transgenic mice. , 1990 .

[24]  J. Ashwell,et al.  Genetic and mutational analysis of the T-cell antigen receptor. , 1990, Annual review of immunology.

[25]  T. Tadakuma,et al.  Activation of murine T cells by toxic shock syndrome toxin-1. The toxin-binding structures expressed on murine accessory cells are MHC class II molecules. , 1989, Journal of immunology.

[26]  H. Rammensee,et al.  Clonal anergy induced in mature Vβ6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells , 1989, Nature.

[27]  R. Cook,et al.  Class II MHC molecules are specific receptors for staphylococcus enterotoxin A. , 1989, Science.

[28]  J. Fraser.  High-affinity binding of staphylococcal enterotoxins A and B to HLA-DR , 1989, Nature.

[29]  H. Sjögren,et al.  Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines. , 1989, Journal of immunology.

[30]  R. Schwartz,et al.  Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. , 1989, Annual review of immunology.

[31]  E. Engleman,et al.  Evidence for an association between CD8 molecules and the T cell receptor complex on cytotoxic T cells. , 1987, Journal of immunology.

[32]  R. Klausner,et al.  Internalization and cycling of the T cell antigen receptor. Role of protein kinase C. , 1987, The Journal of biological chemistry.

[33]  M. Krangel.  Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation , 1987, The Journal of experimental medicine.

[34]  C. Fathman,et al.  Modulation of CD4 by antigenic activation. , 1987, Journal of immunology.

[35]  B. Gallis,et al.  Rapid phosphorylation and modulation of the T4 antigen on cloned helper T cells induced by phorbol myristate acetate or antigen. , 1986, The Journal of biological chemistry.

[36]  B. Tycko,et al.  Segregation of transferrin to a mildly acidic (pH 6.5) para-golgi compartment in the recycling pathway , 1984, Cell.

[37]  J. Lamb,et al.  Tolerance of T-cell clones is associated with membrane antigen changes , 1983, Nature.

[38]  R. Klausner,et al.  Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[39]  A. Ciechanover,et al.  pH and the recycling of transferrin during receptor-mediated endocytosis. , 1983, Proceedings of the National Academy of Sciences of the United States of America.