T-cell receptor peptide immunization leads to enhanced and chronic experimental allergic encephalomyelitis.

Desquenne-Clark, Lise; Esch, Thomas R.; Ötvös, László; Heber‐Katz, Ellen

doi:10.1073/pnas.88.16.7219

Cited by 41 publications

(21 citation statements)

References 15 publications

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“…In close correlation with our data, the TcR peptide-mediated enhancement of EAE observed in this last work was manifested by an early onset of clinical signs and an increase in the severity and duration of EAE. Thus, in agreement with Desquenne-Clark et al [56] using the EAE model,we emphasize that this type of immunization is not a reliable method for inducing suppression of CIA.…”

Section: Discussionsupporting

confidence: 92%

“…Our striking findings that the very same T cell clone reactive to CII possesses the potentiality to either enhance or suppress CIA are closely reminiscent of contradictory studies performed in two different groups using the EAE model. Indeed, Vandenbark et al [54] provided evidence of disease suppression in rats after immunization with a peptide of the CDR2-Vp8 region of the TcR specific for the MBP peptide 72-89 whereas Desquenne-Clark et al [56], using the same experimental system and peptide, observed an exacerbation of the disease. In close correlation with our data, the TcR peptide-mediated enhancement of EAE observed in this last work was manifested by an early onset of clinical signs and an increase in the severity and duration of EAE.…”

Section: Discussionmentioning

confidence: 97%

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T cell regulation of collagen‐induced arthritis in mice. III. Is T cell vaccination a valuable therapy?

et al. 1994

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Since T cells play a critical role in collagen-induced arthritis (CIA), CD4+ T cell hybridomas were derived from DBA/1 mice immunized with bovine type II collagen (CII). The hybrid clones selected were Thy-1-2+, CD4+, CD8-, T cell receptor (TcR) alpha beta + and produced interleukin-2 in response to CII peptides presented by I-Aq molecules. The clones were collagen type-specific and recognized CII from many species except the mouse. More precisely, the reactivity was directed against the immunodominant cyanogen bromide-cleaved fragment CB11(II). Analysis of the TcR carried by the T cell hybridomas showed that they used identical V alpha and J alpha (V alpha BMB, J alpha 20) gene segments and two distinct V beta (V beta 1 and V beta 4) associated with the J beta 2.5 gene segment. Interestingly, the junctional regions were highly conserved in structure and length. These findings may indicate a strong in vivo selection by the antigen for a particular combination of both alpha and beta chains of the TcR. Inoculation of irradiated anti-CII T cell hybrids into DBA/1 mice, before priming with CII, altered the course of the disease resulting in either a long-lasting suppression or an exacerbation of CIA whereas a control CD4+ hybridoma with an unrelated specificity did not influence the development of arthritis. However, the regulatory effect of anti-CII T cell clones was unpredictable, suggesting that the TcR structure may not solely account for the modulation of CIA and that T cell vaccination is not a reliable method for inducing suppression of CIA.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

T cell regulation of collagen‐induced arthritis in mice. III. Is T cell vaccination a valuable therapy?

et al. 1994

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“…Subsequent to Offner et al's (1991) study with the Vp8 CDR2 peptide, Desquenne-Clark et al (1991) demonstrated that immunization with CDR2 peptide frequently led to enhancement of EAE, in contrast to the some sequence similarities between the EAE CP (to MBP 72-82) and TCR and MHC I1 molecules were found; but the physiological relevance of these similarity matches is not clear.…”

Section: Effect Of Eae Cp On Induction Of Eaementioning

confidence: 90%

Studies on T‐cell receptors involved in experimental autoimmune encephalomyelitis using the complementary peptide recognition approach

Chen

Simmons²,

Willenborg³

et al. 1995

J of Neuroscience Research

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Based upon Blalock's complementary recognition approach, a complementary or antisense peptide (CP) was designed to the experimental autoimmune encephalomyelitis (EAE) epitope peptide, rat myelin basic protein (MBP) peptide 72-82. This peptide (EAE CP) was shown to have some sequence similarities to T-cell receptors (TCR) and MHC II molecules in a sequence homology search. Solid-phase binding assays demonstrated specific and high affinity binding (3 and 4 microM) between the EAE CP and the rat and guinea pig EAE epitope peptides (Rt72-82 and Gp69-82), respectively. This EAE CP was also found to be immunogenic in rats in an ear swelling test for delayed type hypersensitivity (DTH) reactions and an ELISA for antibody responses. However, a rabbit antibody generated to EAE CP was shown to be unable to stain the V beta 8+ EAE susceptible T-cells in immunofluorescence analyses. This EAE CP was also used in attempts to down-regulate EAE and the results showed that prior immunization with EAE CP in complete Freund's adjuvant could not prevent the Lewis rats from developing EAE. Although the data on sense-antisense peptide interaction were positive and the EAE CP was immunogenic, the inability of EAE CP to regulate EAE indicates that the CP approach may not be generally applicable.

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“…Third, when the fragment is produced in subtolerogenic amounts by processing, the corresponding synthetic peptide will induce an immune response that could affect the cells naturally presenting this sequence, in the first place, the T cells expressing the appropriate receptor. When the latter cells are involved in autoimmune pathology, a response to them could modify the disease in two possible ways: downregulation with a beneficial effect (9,22), or upregulation leading to exacerbation (27). Future research will have to identify ways to direct the anti-TCR response toward beneficial effects.…”

Section: Discussionmentioning

confidence: 99%

Self tolerance to T cell receptor V beta sequences.

Vidovic

Ward

Bolin

et al. 1995

The Journal of Experimental Medicine

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SummaryT cell tolerance to self is achieved by deletion or inactivation of clones recognizing peptides of self proteins presented by major histocompatibility complex molecules. A considerable fraction of self proteins accessible to the immune system is contributed by the system itself, for example, the receptors used for antigen recognition (antibodies and T cell receptors [TCKs]). Thus far, it has remained unclear, whether antigen receptors are subject to self tolerance, or on contrary, engage into network interactions implying immunity rather than tolerance. In this study, we demonstrate self tolerance to synthetic peptides corresponding to the first hypervariable region of the V~ 8.1 and VB 8.2 TCK proteins. We also show that the tolerogenic synthetic peptide corresponds to a fragment produced by processing of the V/3 protein, and conversely, that a V~ peptide not produced by processing is also not subject to self tolerance. Thus, the rules of tolerance seem to apply to antigen receptors, at least to their germline-encoded portions, in a similar fashion as to other self proteins. This finding has important implications for studies of natural and artificially induced immune networks. Discrimination between self and nonself is a salient feature of the immune system. At the T cell level, this is achieved by inactivation and/or deletion of clones recognizing peptides of self proteins presented by MHC molecules (1-5). Part of the diverse array of self proteins accessible to the immune system is provided by the system itself, for example, the receptors (antibodies and TCR) used for antigen recognition. Nevertheless, self tolerance to antigen receptors has not been demonstrated thus far. In contrast, network interactions implying immunity rather than tolerance to self receptors have been postulated and reported (6-9). We therefore designed an experimental model that could, in principle, answer the question of whether self tolerance to antigen receptors operates under physiological conditions. Our approach has been to investigate the immunogenicity of peptides that are unique to TCK V~ proteins that are expressed in certain mouse strains but not in others. The defect in expressing these proteins can be twofold: first, a large genomic deletion of 50% of V~ genes from chromosome 6 referred to as the TCK-V~ a allele, carried by several inbred mouse strains (10), and second, clonal deletion of T cells expressing particular V~ proteins by endogenous superantigens (1, 2) early in ontogeny in the thymus. Mice expressing or deleting a particular VB were immunized with synthetic peptides derived from that V~ sequence, and a correlation was sought between the pattern of responsiveness and the expression of the V/3 protein. We report here self tolerance to sequences corresponding to the first hypervariable region of the V~ 8.1 and V~ 8.2 proteins. Materials and MethodsMice and Immunizations. Mice were obtained from The Jackson Laboratories (Bar Harbor, ME), except strain B10.Q-V/~' (obtained from Dr. C. David, Mayo Clinic, Roch...

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T-cell receptor peptide immunization leads to enhanced and chronic experimental allergic encephalomyelitis.

Cited by 41 publications

References 15 publications

T cell regulation of collagen‐induced arthritis in mice. III. Is T cell vaccination a valuable therapy?

T cell regulation of collagen‐induced arthritis in mice. III. Is T cell vaccination a valuable therapy?

Studies on T‐cell receptors involved in experimental autoimmune encephalomyelitis using the complementary peptide recognition approach

Self tolerance to T cell receptor V beta sequences.

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