Immunoglobulin‐specific T‐B cell interaction

Yurin, V. L.; Rudensky, Alexander Y.; Mazel, Svetlana; Blechman, Janna

doi:10.1002/eji.1830190924

Cited by 41 publications

(8 citation statements)

References 30 publications

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“…B cells process surface as well as endogenous forms of Ig that are neither expressed on the cell surface nor secreted, and some of the resulting peptides are presented by class H to T cells (10)(11)(12)(13). Processing and presentation of endogenous Ig by class II must be an efficient process since naturally processed Ig peptides are readily eluted from class II molecules (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…Processing and presentation of endogenous Ig by class II must be an efficient process since naturally processed Ig peptides are readily eluted from class II molecules (24)(25)(26). Accordingly, self-Ig V region peptides may participate in shaping the T cell repertoire as well as playing an important role in immune regulation (10)(11)(12)(13)27 proliferation of BWF1 T cells to the whole molecule is detectable, but it is weaker than the response to the immunodominant peptide (28).…”

Section: Discussionmentioning

confidence: 99%

“…IgG anti-DNA production is dependent on autoreactive T cell help (6)(7)(8)(9). Since B cells are capable of processing their own Ig and presenting the resultant peptides to T cells via their MHC class II molecules (10)(11)(12)(13), autoAb molecules might contain increased numbers of T cell determinants which can be recognized by T cells from genetically predisposed autoimmune individuals. The activated T cells would then provide help for continuing synthesis of those autoAbs.…”

Section: Introductionmentioning

confidence: 99%

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Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus.

Singh

Ebling²,

Sercarz³

et al. 1995

J. Clin. Invest.

100

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Mechanisms that initiate and maintain autoantibody (autoAb) production in individuals with autoimmune diseases like SLE are poorly understood. Inadequate suppression of autoreactive T cells and/or unusual activation of T and B cells may underlie the persistence of pathogenic autoAbs in lupus. Here, we examine the possibility that in mice with lupus, autoAb molecules may be upregulating their own production by activating self-reactive T cells via their own processed peptides; downregulation of this circuit may decrease autoAb production and delay the development of lupus. We found that before the onset of clinical disease, lupus-prone (NZB/NZW) F1 [BWF1] (but not MHCmatched nonautoimmune mice) developed spontaneous T cell autoimmunity to peptides from variable regions of heavy chains (V H) of syngeneic anti-DNA mAbs but not to peptides from the V H region of an mAb to an exogenous antigen. Tolerizing young BWF1 mice with intravenous injections of autoAb-derived determinants substantially delayed development of anti-DNA antibodies and nephritis and prolonged survival. Thus, in such an autoAb-mediated disease, the presence of autoreactive T cells against V H region determinants of autoAbs may represent an important mechanism involved in the regulation of autoimmunity. Our findings show that tolerizing such autoreactive T cells can postpone the development of an autoimmune disease like

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus.

Singh

Ebling²,

Sercarz³

et al. 1995

J. Clin. Invest.

100

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“…19, 20, 21, 22, 23 Productive, cognate interactions between immunoglobulin allotype-specific helper T cells and B cells in rodents have been demonstrated in vitro . 24, 25, 26, 27 Therefore, a CD4+ T helper cell epitope in the constant region of an exogenously administered antibody could potentially support the development of antibody responses to other novel regions of the protein, as exemplified by the complementarity determining regions, in humans. In such an example, antibodies specific for the G1m1 sequence may be undetectable but a specific CD4+ helper T-cell response could be present.…”

Section: Introductionmentioning

confidence: 99%

The human G1m1 allotype associates with CD4+ T-cell responsiveness to a highly conserved IgG1 constant region peptide and confers an asparaginyl endopeptidase cleavage site

et al. 2011

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The human G1m1 allotype comprises two amino acids, D12 and L14, in the CH3 domain of IGHG1. Although the G1m1 allotype is prevalent in human populations, ∼40% of Caucasiods are homozygous for the nG1m1 allotype corresponding to E12 and M14. Peptides derived from the G1m1 region were tested for their ability to induce CD4+ T-cell proliferative responses in vitro. A peptide immediately downstream from the G1m1 sequence was recognized by CD4+ T cells in a large percentage of donors (peptide CH315−29). CD4+ T-cell proliferative responses to CH315−29 were found at an increased frequency in nG1m1 homozygous donors. Homozygous nG1m1 donors possessing the HLA-DRB1*07 allele displayed the highest magnitudes of proliferation. CD4+ T cells from donors homozygous for nG1m1 proliferated to G1m1-carrying Fc-fragment proteins, whereas CD4+ T cells from G1m1 homozygous donors did not. The G1m1 sequence creates an enzymatic cleavage site for asparaginyl endopeptidase in vitro. Proteolytic activity at D12 may allow the presentation of the CH315−29 peptide, which in turn may result in the establishment of tolerance to this peptide in G1m1-positive donors. Homozygous nG1m1 patients may be more likely to develop CD4+ T-cell-mediated immune responses to therapeutic antibodies carrying the G1m1 allotype.

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“…Evidence has also been provided for I-E-restricted B cell presentation of mouse Ig VHh2315 peptides to idiotopespecific CD4' T clones [ 11. Rat B cells have been shown to present Cxb-derived peptides to helper-inducer T cell clones in the context of RT-1B (I-A-like) class I1 molecules [3,4]. There are also indications for the existence of mouse class II-restricted antigen-specific CD4' or CD8' CTL suppressing the humoral response [6, 71.…”

Section: H-2dbmentioning

confidence: 99%

The T/B cell interaction involved in induction of the mouse IgG2a^h suppression is restricted by major histocompatibility complex class I, but not class II molecules

Majlessi

Bordenave

1997

Eur J Immunol

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To determine the major histocompatibility complex (MHC) restriction of the T/ B cell interaction involved in a negative regulation of Ig production, we used mouse model of T cell-induced IgG2ab suppression in vivo. Normal or specifically triggered T splenocytes from mice of the Igha haplotype, when neonatally transferred into histocompatible Igha/b heterozygotes, are able to induce a specific and total suppression of the IgG2ab allotype. Nevertheless, only transfer of IgG2ab-primed Igha T splenocytes induces this suppression in Ighb/b homozygous congenic mice in which the whole IgG2a isotype production is inhibited. This suppression is chronically maintained by CD8+ T cells, but can be experimentally reversed. We have established that the suppression induction required a CD4+CD8+ T cell cooperation and operated via the recognition by the involved TCR of C gamma 2ab-derived peptides presented by the target B cells in an MHC haplotype-restricted manner. Here, by using Ighb mice genetically deficient for MHC class I (beta 2-microglobulin%, or beta 2m%) or class II (I-A beta%) molecules, we demonstrate functionally that the suppression induction implicates an MHC class I-, but not class II-restricted interaction. Indeed, the anti-IgG2ab T cells transferred into Ighb H-2b I-A beta% mice carry out the suppression process normally, while in Ighb H-2b beta 2m% recipients, their suppression induction capacity is significantly inhibited. Moreover, the C gamma 2ab 103-118 peptide, identified as the sole C gamma 2ab-derived peptide able to amplify the anti-IgG2ab T cell reactivity in Igha H-2b mice, is also able to stabilize the H-2Db, but not the H-2Kb class I molecules at the surface of RMA-S (TAP2-, H-2b) cells. These results indicate that, despite the CD4+/CD8+ T cell cooperation during the induction phase of suppression only MHC class I molecule expression is required at the surface of IgG2ab+ B cells for suppression establishment.

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Immunoglobulin‐specific T‐B cell interaction

Cited by 41 publications

References 30 publications

Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus.

Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus.

The human G1m1 allotype associates with CD4+ T-cell responsiveness to a highly conserved IgG1 constant region peptide and confers an asparaginyl endopeptidase cleavage site

The T/B cell interaction involved in induction of the mouse IgG2a^h suppression is restricted by major histocompatibility complex class I, but not class II molecules

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Immunoglobulin‐specific T‐B cell interaction

Cited by 41 publications

References 30 publications

Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus.

Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus.

The human G1m1 allotype associates with CD4+ T-cell responsiveness to a highly conserved IgG1 constant region peptide and confers an asparaginyl endopeptidase cleavage site

The T/B cell interaction involved in induction of the mouse IgG2ah suppression is restricted by major histocompatibility complex class I, but not class II molecules

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The T/B cell interaction involved in induction of the mouse IgG2a^h suppression is restricted by major histocompatibility complex class I, but not class II molecules