Document 0195
 DOCN  M9650195
 TI    Definition of sites on HLA-DR1 involved in the T cell response to
       staphylococcal enterotoxins E and C2.
 DT    9605
 AU    Hargreaves RE; Brehm RD; Tranter H; Warrens AN; Lombardi G; Lechler RI;
       Department of Immunology, Royal Postgraduate Medical School,;
       Hammersmith Hospital, London, GB.
 SO    Eur J Immunol. 1995 Dec;25(12):3437-44. Unique Identifier : AIDSLINE
       MED/96140684
 AB    We have exploited the relative inefficiency of interaction between
       staphylococcal enterotoxins, SEE or SEC2, and H-2Ek compared to HLA-DR1
       molecules to deduce which regions of the major histocompatibility
       complex (MHC) class II molecule are involved in the T cell response to
       these superantigens. Transfectants expressing hybrid DR/H-2E MHC class
       II molecules were used to present SEE to the T cell receptor V beta
       8.1-expressing Jurkat cell line, and SEC2 to human peripheral blood T
       cells. For SEE, the critical region of the class II molecule for T cell
       reactivity and for binding was the beta 1 domain alpha-helix. The
       functional data were corroborated by measurements of direct binding.
       Sequence comparison between DR and H-2E raised the possibility that the
       glutamic acid at position 84 in the beta chain of H-2Ek, in place of
       glycine was responsible for the observed functional effects. This
       suggestion was supported by the finding that DQw2 (glutamine at 84)
       transfectants supported the SEE response much more efficiently than DQw6
       that has glutamic acid at this position. In addition, amino acid
       substitutions at either position 36 or 39 in the DR alpha 1 domain
       abolished T cell reactivity without any obvious alteration in binding.
       For SEC2, use of transfectants expressing exon-shuffled alpha and beta
       chain genes showed that replacement of the alpha 1, alpha 2 and beta 1
       domains with H-2E sequence inhibited the presentation of SEC2.
       Similarly, the substitutions at positions 36 and 39 in the alpha 1
       domain abolished the T cell response to SEC2. Taken together, these data
       may be best explained by a model in which these two toxins have primary
       binding sites on the beta 1 domain (SEE) and the alpha 1 and alpha 2
       domains (SEC2), but by virtue of a secondary binding site on the
       opposite surface of the class II molecule, cross-link two adjacent DR
       molecules. Such cross-linking may be important in the induction of T
       cell reactivity.
 DE    Amino Acid Sequence  Antigen Presentation  Clone Cells  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/IMMUNOLOGY
       Enterotoxins/*IMMUNOLOGY  H-2 Antigens/IMMUNOLOGY  Human  HLA-DR1
       Antigen/CHEMISTRY/GENETICS/*IMMUNOLOGY  Lymphocyte Transformation
       Molecular Sequence Data  Protein Binding  Protein Conformation
       Staphylococcus aureus/*IMMUNOLOGY  Superantigens/*IMMUNOLOGY  Support,
       Non-U.S. Gov't  T-Lymphocytes/*IMMUNOLOGY  Transfection  Tumor Cells,
       Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).