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R J Ely

Publications and source records attributed to R J Ely.

4 recordsLinked to original sources

Vbeta-dependent stimulation of bovine and human T cells by host-specific staphylococcal enterotoxins.

Staphylococcus aureus isolates from bovine and ovine species produce unique molecular variants of type C staphylococcal enterotoxin (SEC). The SEC animal variants have greater than 98% amino acid sequence identity with SEC1, a human-associated SEC. The two SEC animal variants have been designated SEC(bovine) and SEC(ovine) according to their corresponding host species. We showed previously that these toxins induce quantitatively different levels of T-cell stimulation in several animal species. The present study compared the abilities of these closely related host-specific SEC variants to stimulate Vbeta-bearing T cells from bovine and human donors. All three toxins expanded human T cells bearing T-cell receptor Vbeta elements (huVbeta) 3, 12, 13.2, 14, 15, 17, and 20. However, SEC1 resulted in greater expansion of hyVbeta12 than either SEC(bovine) or SEC(ovine). In addition, bovine T cells proliferate in a Vbeta-dependent manner in response to these superantigens (SAgs). All three toxins induced the proliferation of bovine T cells bearing the previously sequenced Vbeta element (boVbeta) from the bovine T-cell clone BTB13 (boVbetaBTB13). SEC1 and SEC(ovine) also were able to induce proliferation of bovine T cells bearing boVbetaBTB35, which SEC(bovine) failed to stimulate. The species-specific differences in T-cell proliferation exhibited by these closely related SEC variants may reflect the evolutionary adaptation of S. aureus, presumably to increase its host range by the manipulation of the immune system in a host-specific manner.

Amino Acid Sequence↗

Subtype-specific interactions of type C staphylococcal enterotoxins with the T-cell receptor.

The goal of this study was to investigate the molecular interaction between superantigens and the T-cell receptor (TCR). Using a quantitative polymerase chain reaction (PCR) to assess T-cell proliferation profiles, we found that SEB, SEC1, SEC2 and SEC3 expanded human T cells bearing V beta 3, V beta 12, V beta 13.2, V beta 14, V beta 15, V beta 17 and V beta 20. SEC2 and SEC3 have the additional ability to expand T cells bearing V beta 13.1, and their expansion of V beta 3 was markedly reduced compared to SEB and SEC1. Based on the activity of SEC1 mutants containing single amino acid substitutions, we concluded that the differential abilities of these native toxins to stimulate V beta 3 and V beta 13.1 was determined by the residue in position 26, located in the base of the SEC alpha 3 cavity. The SEC1 mutant, in which Val in position 26 was substituted with the analogous SEC2/SEC3 residue (Tyr), generated a V beta expansion profile that was indistinguishable from those generated by SEC2 and SEC3. Using these findings, the co-ordinates of a recently reported murine TCR beta-chain crystal structure, and other documented information, we propose a compatible molecular model for the interaction of SEC3 with the T-cell receptor. In this model complex, the complementarity-determining regions (CDRs) 1 and 2 and the hypervariable loop 4 of the V beta element contact SEC3 predominantly through residues in the alpha 3 cavity of the toxin. CDR3 of the beta chain is not involved in any toxin contacts. The proposed model not only includes contacts identified in previous mutagenesis studies, but is also consistent with the ability of tyrosine and valine in position 26 to differentially affect the expansion of V beta s 3 and 13.1 by the SEC superantigens.

CD3 Complex↗

A battle of wills: self-verification versus behavioral confirmation.

When a perceiver forms an expectancy about a target individual that is discrepant with that target's self-conception, whose viewpoint will triumph? Although research on behavioral confirmation argues that perceivers will "win" by causing targets to confirm the expectancy, research on self-verification argues that targets will "win" by bringing perceivers to treat them in a manner that confirms their self-conceptions. The research reported here sought to reconcile these competing viewpoints by considering the certainty of perceivers' expectancies and targets' self-conceptions. Perceivers first formed relatively certain or uncertain expectancies about targets that were inconsistent with targets' self-conceptions. They then interacted with targets, who possessed relatively certain or uncertain self-conceptions, in a series of three successive interview sessions. Analyses of the behavior or targets indicated that self-verification always occurred when targets were certain of their self-conceptions. Self-verification also tended to occur when both perceivers and targets were uncertain of their beliefs. Behavioral confirmation tended to occur only when perceivers were certain of their expectancies and targets were uncertain of their self-conceptions. At the end of the experiment, perceivers had generally abandoned their expectancies, but targets revealed no self-rating change. The conditions under which self-verification versus behavioral confirmation occur are discussed.

Adult↗