Definition of sites on HLA-DR1 involved in the T cell response to staphylococcal enterotoxins E and C2
✍ Scribed by Roseanna E. G. Hargreaves; Rossalyn D. Brehm; Howard Tranter; Anthony N. Warrens; Giovanna Lombardi; Robert I. Lechler
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 876 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Definition of sites on HLA-DR1 involved in the T cell response to staphylococcal enterotoxins E and c2
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 I1 molecule are involved in the T cell response to these superantigens. Transfectants expressing hybrid DWH-2E MHC class I1 molecules were used to present SEE to the T cell receptor VP8.1-expressing Jurkat cell line, and SEC2 to human peripheral blood T cells. For SEE, the critical region of the class I1 molecule for T cell reactivity and for binding was the 61 domain a-helix. The functional data were corroborated by measurements of direct binding. Sequence comparison between D R and H-2E raised the possibility that the glutamic acid at position 84 in the P 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 D R a l domain abolished T cell reactivity without any obvious alteration in binding. For SEC2, use of transfectants expressing exon-shuffled a and P chain genes showed that replacement of the al, a2 and 61 domains with H-2E sequence inhibited the presentation of SEC2. Similarly, the substitutions at positions 36 and 39 in the a1 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 81 domain (SEE) and the a1 and a2 domains (SEC2), but by virtue of a secondary binding site on the opposite surface of the class I1 molecule, cross-link two adjacent DR molecules. Such cross-linking may be important in the induction of Tcell reactivity.