Synthetic peptides and β‐chain gene rearrangements reveal a diversified T cell repertoire for a λ light chain third hypervariable region

Bogen, Bjarne; Snodgrass, Ralph; Briand, Jean Paul; Hannestad, Kristian

doi:10.1002/eji.1830161111

Cited by 57 publications

(57 citation statements)

References 25 publications

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“…In the 1980s it became clear that immunoglobulins are processed and presented by antigen-presenting cells (APC) and that V-region-derived Id-peptides are displayed on MHC class II molecules to Id-specific CD4 + T cells [5][6][7][8]. It was further demonstrated that B cells continuously processed their own BCR and constitutively presented Id-peptides on their MHC class II molecules [9][10][11] [12].…”

Section: Id-specific T Cells Recognize V-region Sequence Determinantsmentioning

confidence: 99%

Review: To What Extent are T Cells Tolerant to Immunoglobulin Variable Regions?

Bogen

Ruffini

2009

Scand J Immunol

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Id-specific B cells recognize conformational determinants on complete Ig-moleculesImmunoglobulin V-regions are extremely diversified due to V(D)J recombination and somatic hypermutation [1]. Thus, immunoglobulin V-regions probably represent the largest collection of diverse antigenic determinants on self molecules within the body. B cell recognition of such Id determinants depend on association of L-and H-chain V-regions, which enormously increases the number of serological Id determinants expressed on Ig molecules in the body [2]. It has been argued that the immune system cannot be tolerant to all these conformational Id determinants, otherwise, dangerous holes in the B-cell repertoire for external antigens, such as viruses, would be generated. The lack of B-cell tolerance to V-region antigenic determinants is supported by the observation that immunization with monoclonal Ig readily generates anti-Id antibodies in an individual [3], which is the basis for Jerne's Network theory [4]. Id-specific T cells recognize V-region sequence determinants displayed on MHC moleculesSo what about T cell recognition of Id? In the 1980s it became clear that immunoglobulins are processed and presented by antigen-presenting cells (APC) and that V-region-derived Id-peptides are displayed on MHC class II molecules to Id-specific CD4 + T cells [5][6][7][8]. It was further demonstrated that B cells continuously processed their own BCR and constitutively presented Id-peptides on their MHC class II molecules [9][10][11] [12]. Thus, B cells express two types of Id: (1) conformational Id determinants expressed on intact BCR, serologically detected by anti-Id antibodies and (2) short Id-peptides that are presented on MHC class II molecules to Id-specific T cells [9]. Id-peptide ⁄ MHC II presentation to CD4 + T cells represented at that time a novel type of interaction between T and B cells in the absence of external antigen, and it was suggested that such Id-driven T-B collaboration could play a role in immune regulation, autoimmunity and memory [13]. Later, similar ideas were expressed by others [14,15]. Id-specific T cells in immune regulation and diseaseThis hypothesis has gained support from experiments where Id-driven T-B collaboration was made chronic by use of 'paired' Ig and TCR-transgenic mice as sources of Id + B cells and CD4 + T cells respectively. Perpetual Id-driven T-B collaboration was shown to result in We argue that T cells are to a large extent tolerant to germline-encoded V-region sequences but that there is a T-cell repertoire for rare Id-sequences that arise as a consequence of somatic hyper mutation or N-region diversity. Moreover, when otherwise rare Id-sequences increase in concentration, T-cell tolerance is induced (Fig. 1). For these reasons, T cells that recognize rare Id-peptides, arising as a consequence of somatic genetic events unique to each B cell, may play a special importance in Id-driven T-B collaboration, immunosurveillance of B-cell malignancies, and Id-vaccination.

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Section: Id-specific T Cells Recognize V-region Sequence Determinantsmentioning

confidence: 99%

Review: To What Extent are T Cells Tolerant to Immunoglobulin Variable Regions?

Bogen

Ruffini

2009

Scand J Immunol

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“…To test this directly we have used recently established T-cell clones specific for an idiotope of A2315 in the context of the I-Ed MHC antigen (7,8). These clones, like the T cells studied in vivo before (4, 5), recognize an idiotypic determinant on A2315 around amino acid positions 94, 95, and 96 (7, 8 …”

Section: Introductionmentioning

confidence: 99%

“…This proposal was based on the findings that T cells specific for an idiotype on the A2 light chain from MOPC315 cells (A2315) recognized denatured forms of A2315 (4) and that this recognition was under H-2-linked immune response (Ir) gene control (5). The hypothesis has been supported and extended by later work (6)(7)(8). Similar ideas have recently been proposed by others (9,10), and MHC-restricted T cells specific for idiotypes (11,12) and allotypes (13) have been described.…”

mentioning

confidence: 99%

“…Similar ideas have recently been proposed by others (9, 10), and MHC-restricted T cells specific for idiotypes (11,12) and allotypes (13) have been described. However, it is still unclear whether MHC-restricted T cells recognize processed forms of immunoglobulin exclusively and whether B cells can process their own immunoglobulin.To test this directly we have used recently established T-cell clones specific for an idiotope of A2315 in the context of the I-Ed MHC antigen (7,8). These clones, like the T cells studied in vivo before (4, 5), recognize an idiotypic determinant on A2315 around amino acid positions 94, 95, and 96 (7, 8 …”

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confidence: 99%

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B-lymphoma cells process and present their endogenous immunoglobulin to major histocompatibility complex-restricted T cells.

Weiß

Bogen

1989

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

199

137

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Antigen-presenting B-lymphoma cells were transfected with the gene encoding the immunoglobulin A2 light chain of MOPC315 cells (A2315). The A2 chain is expressed on the cell surface of the transfectants together with the endogenous heavy chain. (4) and that this recognition was under H-2-linked immune response (Ir) gene control (5). The hypothesis has been supported and extended by later work (6-8). Similar ideas have recently been proposed by others (9, 10), and MHC-restricted T cells specific for idiotypes (11,12) and allotypes (13) have been described. However, it is still unclear whether MHC-restricted T cells recognize processed forms of immunoglobulin exclusively and whether B cells can process their own immunoglobulin.To test this directly we have used recently established T-cell clones specific for an idiotope of A2315 in the context of the I-Ed MHC antigen (7,8). These clones, like the T cells studied in vivo before (4, 5), recognize an idiotypic determinant on A2315 around amino acid positions 94, 95, and 96 (7, 8

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“…Probes 11M1, 11M2, and 13F1 were isolated from cosmid clone TA 28 .1 (34). Probe IOFI is a 3.0-kb Barn HI fragment isolated from the genomic (EMBL) clone 4B2A1-a-2 (35) . Ja region probes 4,5,7,8,10, and 16(Cb) were kindly provided by Drs.…”

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confidence: 99%

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Falcioni¹,

Dembić²,

Müller³

et al. 1990

The Journal of Experimental Medicine

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Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.

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Synthetic peptides and β‐chain gene rearrangements reveal a diversified T cell repertoire for a λ light chain third hypervariable region

Cited by 57 publications

References 25 publications

Review: To What Extent are T Cells Tolerant to Immunoglobulin Variable Regions?

Review: To What Extent are T Cells Tolerant to Immunoglobulin Variable Regions?

B-lymphoma cells process and present their endogenous immunoglobulin to major histocompatibility complex-restricted T cells.

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

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