T-cell repertoires in healthy and diseased human tissues analysed by T-cell receptor β-chain CDR3 size determination: evidence for oligoclonal expansions in tumours and inflammatory diseases

Even, Jos; Lim, Annick; Puisieux, Isabelle; Ferradini, Laurent; Py, Dietrich; Toubert, Antoine; Hercend, Thierry; Triebel, Frédéric; Pannetier, Christophe; Kourilsky, Philippe

doi:10.1016/0923-2494(96)80240-9

Cited by 105 publications

(73 citation statements)

References 47 publications

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“…In vivo clonality of the Vc4/ Vd5 + population was then explored in bulk PBMC by the analysis of CDR3 length distribution of TCR d chain using the immunoscope method [19]. A unique Vd5-Cd junctional length (164 bp-long fragment primer to primer) was amplified, establishing that this subset of cells was monoclonal in vivo (Fig.…”

Section: Resultsmentioning

confidence: 99%

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

et al. 2005

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NK cell receptors for MHC class I molecules (MHC-NKR) can be expressed by T cell subsets. The restricted repertoire and phenotypic characteristics of MHC-NKR + T cells indicate that expression of MHC-NKR is acquired upon antigenic challenge and might promote expansion of T cells. Previous studies performed on in vitro generated ab T cell clones concluded that MHC-NKR expression was not a clonal attribute. Here, we examined a massive monoclonal expansion of a non-leukemic cd T cell population found in the peripheral blood of a lung-transplanted patient who suffered from a cytomegalovirus infection. Despite their monoclonality, these T cells displayed a heterogeneous and stable in vivo Ig-and lectin-like MHC-NKR phenotype. Twenty percent of the cells displayed a CD94 + NKG2A + phenotype, and 10% were labeled with an anti-CD158b1/b2/j monoclonal antibody. A CD158b/j + cd T cell clone derived in vitro from patient's peripheral blood lymphocytes was shown to express the activating form CD158j (KIR2DS2), which once cross-linked stimulated the clone cytolytic function and costimulated the TCR-induced production of cytokines, independently of the killer-activating receptor-associated protein (KARAP). In conclusion, heterogeneity of MHC-NKR expression confers a functional intraclonal diversity that may participate to induction of specific cd T cell effector functions or proliferation upon pathogen challenge.

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Section: Resultsmentioning

confidence: 99%

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

et al. 2005

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“…Immunoscope analysis was performed with a modified protocol. 27,35 A measure of 2 ml of BV14-BC or BV16-BC PCR products were used as templates and run-off reactions were performed with a single internal fluorescent label for each of the 6FAM (expand)-labeled BC or BJ primers ( Table 5). The reaction profile consisted of 30 s at 941C denaturation temperature and 15 cycles at 941C for 45 s; at 551C for 45 s, at 721C for 1 min, followed by 721C for 5 min as an extension step.…”

Section: Immunoscope Analysismentioning

confidence: 99%

“…Multiple CDR3 sizing peaks typically found in synovial TCR transcripts of RA require several hundreds to thousands of measurements for each sample when multiplied by the number of BV and BJ genes (25 BV and 13 BJ genes), to characterize clonotypes of interest. 27 This study was undertaken to examine the BV usage pattern of infiltrating T cells derived from synovial material of a cohort of Chinese RA patients whose HLA background differed from that of Caucasian patients to determine potential association of BV gene distribution with HLA. It was attempted to identify common clonotypes and CDR3 structural characteristics in overexpressed BV transcripts of synovial T cells from different RA patients.…”

Section: Introductionmentioning

confidence: 99%

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Sun

Nie²,

et al. 2005

Genes Immun

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T-lymphocytes play an important role in rheumatoid arthritis (RA). In this study, we evaluated the hypothesis that common T-cell receptor (TCR) structural features may exist among infiltrating T cells of different RA patients, if the TCR repertoire is shaped by interaction with common self or microbial antigens in the context of susceptible HLA genes in RA. Synovial lesion tissue (ST), synovial fluid (SF) and blood specimens from RA patients and controls were analyzed for TCR V gene repertoire by real-time PCR. There was highly skewed BV14 and BV16 usage in synovial T cells of RA as opposed to those of controls, which was accompanied with a trend for correlation between skewed BV16 and DRB1*0405. Immunoscope analysis of the V-D-J region of ST-derived T cells demonstrated oligoclonal and polyclonal expansion of BV14 þ and BV16 þ T cells. Detailed characterization using specific BV and BJ primers further revealed common clonotypes combining the same BV14/BV16, BJ and CDR3 length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and CDR3 structural characteristics among synovial infiltrating T cells of RA.

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“…RNA was extracted as previously described (14). Fluorescent DNA products were migrated on sequencing gels in an automated DNA sequencer (Applied Biosystems Inc., Foster City, CA), and raw data were analyzed by the immunoscope software package (15,16).…”

Section: Immunoscope Analysismentioning

confidence: 99%

“…The T cell repertoire of these different T cell populations was further investigated by analyzing the distribution of TCR CDR3 length with a recently described technique termed Im- munoscope (14). This sensitive technique, which involves a combination of PCR and run off reactions using pairs of V ␤ / C ␤ primers followed by size determination of the elongation products, allows efficient detection of oligoclonal T cell expansion within each of the TCRBV subsets studied.…”

Section: Analysis Of T Cell Repertoire Diversity Before and After Tramentioning

confidence: 99%

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

Gaschet¹,

Lim²,

Liem³

et al. 1996

J. Clin. Invest.

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Analysis of a large number of unrelated bone marrow transplantations (BMT) has shown that HLA-DP incompatibility did not detectably influence the risk for acute graft-versushost disease (aGVHD). Accordingly, it was proposed that HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B, or -DR. We have previously shown that HLA-DP (as well as HLA-A, -B, -DQ, or -DR)-specific T cells could be isolated from skin biopsies of patients who developed an aGVHD after semiallogeneic BMT. Nevertheless, whether a single HLA-DP mismatched allele could induce a detectable allo-specific reaction in vivo after BMT remained to be established. To directly address this issue we studied one patient who presented aGVHD after receiving purified CD34 ϩ bone marrow (BM) cells from an unrelated donor with a single HLA-DP mismatch in the GVHD direction. To characterize the immunological events associated with GVHD, we analyzed the peripheral T cell repertoire, the T cell receptor V ␤ diversity, and the specificity of T cells invading a skin biopsy at the onset of GVHD. Our results demonstrated that a large fraction of skin-infiltrating lymphocytes, which expressed diverse T cell receptors, were reactive against this single HLA-DPB1*0501 mismatch and consequently that a single HLA-DP mismatch between BM donor and recipient can activate a strong T cell response in vivo. ( J. Clin. Invest. 1996. 98:100-107.)

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T-cell repertoires in healthy and diseased human tissues analysed by T-cell receptor β-chain CDR3 size determination: evidence for oligoclonal expansions in tumours and inflammatory diseases

Cited by 105 publications

References 47 publications

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.

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