Conventional antigen and superantigen may be coupled to distinct and cooperative T-cell activation pathways.

Liu, Hsi; Lampe, Marilyn A.; Iregui, Maria Victoria; Cantor, Harvey

doi:10.1073/pnas.88.19.8705

Cited by 36 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Peptide and superantigen activate these T-cell responses by forming a trimolecular receptor-ligand complex with the TCR and MHC class II molecule, but the mechanism of activation may differ, as peptide and superantigen interact at spatially distinct regions on the MHC class II molecule and the TCR (7)(8)(9)(10)(11). Consistent with this possibility is evidence that the two ligands induce different intracellular signals (12,13).…”

supporting

confidence: 54%

“…Superantigen and Asn73 APL together, however, resulted in decreased production of inositol phosphates, similar to the antagonism reported for human Th clones and immunogenic peptide (21). Although superantigen and conventional antigen can differ in the signals transduced via the TCR, typical T-cell signals (Ca2+ flux, phosphatidylinositol metabolism and phospholipase C-yl phosphorylation) have been observed following superantigen activation of some T cells (12,13,(32)(33)(34). At least for the induction of phosphatidylinositol turnover, superantigen and conventional antigen appeared to activate similar pathways in our Thl clones.…”

Section: Apls Block the Superantigen Stimulation Of Thi And Th2mentioning

confidence: 75%

See 1 more Smart Citation

Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by altered peptide ligand.

Evavold

Sloan‐Lancaster

Allen

1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

supporting

confidence: 54%

Section: Apls Block the Superantigen Stimulation Of Thi And Th2mentioning

confidence: 75%

Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by altered peptide ligand.

Evavold

Sloan‐Lancaster

Allen

1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Further studies should clarify these issues. Nevertheless, the observations that a conventional antigen and a superantigen induce different cytokine gene expressions in the same T-cell clone (24) and that antigen and superantigen induce additive responses (20) support the theory that intracellular biochemical events initiated by TCR ligation by these two classes of ligands are functionally distinct.…”

Section: Discussionmentioning

confidence: 88%

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

Oyaizu

Chirmule

Yagura

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The role of the CD4 molecule in activation of T-helper cells was examined by investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in conventional peptide antigen-specific cloned T-helper cells that are also reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are CD4+/CD45RO+/T-cell antigen receptor «-chain variable region 12-positive and can respond to nominal peptide antigens and SEB by proliferation in the presence of class II major histocompatibility complex-expressing accessory cells. Although antigen and SEB were comparable in their ability to induce proliferative responses, interleukin 2 (IL-2) production, and IL-2 receptor a-chain expression, stimulatin with SEB failed to trigger phosphatidylinositol hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a treatment inhibited antigen-induced proliferative responses of T cells with concomitant suppression of IL-2 production and IL-2 receptor expression. In contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate that the functional consequences of binding (ligation) of conventional antigen and of superantigen with the T-cell receptor are distinct in the context of both signal transduction pathways and participation of CD4 molecules.Superantigens are molecules that are recognized differently from conventional antigens by responsive T cells. Superantigens are characterized by their ability to bind to a component or components of class II major histocompatibility complex (MHC) molecules and to stimulate T cells in a ,B3chain variable region (V9)-specific manner (1). Conventional antigens bind within a polymorphic groove on class II MHC molecules and interact only with T cells bearing unique a and ,B T-cell antigen receptors (TCRs). Superantigens interact with class II molecules outside the antigen groove (2) and stimulate distinct Vg-expressing T cells (1 Cells. Antigen-specific human T-cell clones specific for tetanus toxoid and for purified protein derivative (PPD) were developed as described (7). The clones used, PPD3.2, PPD3.5, and Tt4.2, express the phenotype CD3+/CD4+/ CD45RO+ (UCHL1+). These clones also react with mAb to V,12 (T Cell Science, Cambridge, MA). They proliferate and secrete IL-2 after stimulation with antigen in the presence of irradiated autologous Epstein-Barr virus-transformed B cells as antigen-presenting cells (APC), designated EBV300 for clones PPD3.2 and PPD3.5 and EBV400 for Tt4.

show abstract

“…However, this was not the case, suggesting that positive selection in the thymus had not directly influenced the fine specificity of the T cells to Mls-1, and supporting the idea that TCR/MHC interactions differ between superantigen and classical peptide recognition. An unconventional TCR/MHC interaction during superantigen engagement might explain reports suggesting that signaling events associated with TCR recognition of superantigen are different from those induced by recognition of conventional antigen/MHC (41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Major histocompatibility complex-specific recognition of Mls-1 is mediated by multiple elements of the T cell receptor.

Woodland

Smith

Surman

et al. 1993

The Journal of Experimental Medicine

View full text Add to dashboard Cite

SummaryWe have recently shown that recognition of the mouse mammary tumor virus 9-associated superantigen (vSAG-9) by routine VB17 ~ T cells is strongly influenced by the major histocompatibility complex (MHC) class II haplotype of the presenting cells, resulting in a form of MHC-restricted recognition. This finding was unexpected, because T cell recognition of another well-characterized retroviral superantigen, minor lymphocyte-stimulating antigen 1 (Mls-1), had been shown to be independent of the MHC haplotype of the presenting cell. To determine whether recognition of vSAG-9 and Mls-1 is fundamentally different, we undertook an extensive analysis of MHC haplotype influences on vSAG-9 and Mls-1 recognition by panels of T cell hybridomas. Our results show that, although most hybridomas recognized Mls-1 regardless of the MHC haplotype of the presenting cells, as previously described by others, some hybridomas exhibited unique patterns of MHC fine specificity. Thus, T cell recognition of vSAG-9 and Mls-1 is not fundamentally different, but the apparent differences can be explained in terms of frequency. The MHC fine specificity of individual Mls-l-reactive hybridomas was influenced by both VB and non-V~/T cell receptor (TCR) elements. First, the influence of the VB element was apparent from the observation that VB8.2 + hybridomas were significantly more MHC specific in their recognition of Mls-1 than V~8.1 hybridomas. Second, a role for the TCR ol chain was implicated from the distinct patterns of fine specificity of Mls-1 reactivity among a panel of transgenic hybridomas that expressed an identical B chain (V/~8.1DB2JB2.3CB2). Sequence analysis revealed that junctional residues of the TCR oe chain and/or Vo~/Jo~ combinations influenced the MHC haplotype fine specificity for Mls-1. Third, D/3J~ influences were implicated, in that the transgenic hybridomas expressed distinctive patterns of Mls-1 fine specificity not represented among V~8.1 + nontransgenic hybridomas. The findings that T cell recognition of endogenous superantigen is MHC specific, and that this specificity correlates with non-V~ elements of the TCR, support the hypothesis that there is a direct interaction between the TCR and either polymorphic residues of the MHC class II molecule or haplotype-specific dominant peptides presented by class II.B acterial and retroviral superantigens are characterized by their ability to stimulate T ceils based predominantly on the expression of specific TCR VB dements (1, 2), although non-V/3 dements of the receptor have recently been shown to have an influence on reactivity (3-6). MHC class II molecules are necessary for presentation of superantigens to T cells, but these responses are not classically MHC restricted, in that individual T cells are able to recognize a single superantigen presented in the context of multiple class II molecules. However, it has been shown that class II isotypes and alleles vary in their effectiveness as presenting molecules. For example, studies with murine clones and hybridomas speci...

show abstract

Conventional antigen and superantigen may be coupled to distinct and cooperative T-cell activation pathways.

Cited by 36 publications

References 32 publications

Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by altered peptide ligand.

Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by altered peptide ligand.

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

Major histocompatibility complex-specific recognition of Mls-1 is mediated by multiple elements of the T cell receptor.

Contact Info

Product

Resources

About