Standardized analysis for the quantification of Vβ CDR3 T-cell receptor diversity

Long, S. Alice; Khalili, Jahan S.; Ashe, Jimiane; Berenson, RJ; Ferrand, Christophe; Bonyhadi, Mark

doi:10.1016/j.jim.2006.09.015

Cited by 29 publications

(27 citation statements)

References 36 publications

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“…In normal circumstances, when the immune system is unaffected by any antigen stimulation, TCR BV is rearranged randomly, and the T cells show a positive polyclonal state. However, in case of disease (Long et al, 2006;Matsumoto et al, 2006;Miqueu et al, 2007), stimulation by specific antigens can cause the targeted rearrangement and excessive abnormal cloning of one or a few of the TCR BV subfamilies, and the dominant form of the cloned T cell may suppress the cloning of other T cells, which may result in a decrease of immune function.…”

Section: Discussionmentioning

confidence: 99%

Preliminary study of the clonal characteristics of the TCR BV subfamilies in T cells in the peripheral blood from patients with uveitis

Zou¹,

Yu²,

Zhang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the characteristics and polymorphisms of the T-cell receptor BV complementaritydetermining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from patients with uveitis to provide an experimental basis for studying the pathogenesis of this disease. RT-PCR amplification of 26 subfamilies of the TCR BV CDR3 gene and immune spectratyping analysis were used to study the pedigree drift of TCR BV CDR3 in PBMCs from the uveitis patients. The following results were obtained: 1) the vast majority of the TCR BV CDR3 spectra in PBMCs in 5 healthy subjects fit the normal (or Gaussian) distribution. The distributions of the TCR BV CDR3 spectra in 4 patients with uveitis were non-normal and showed an abnormal peak including a widowed peak trend, a partial peak, and an irregular abnormal peak. 2) In the 26 TCR BV subfamilies, the abnormal peak frequency was different T-cell receptor and uveitis in the various subfamilies. The BV2 and BV17 (both 3/4) subfamilies had higher frequencies of the non-normally distributed abnormal peak. The BV5.2, BV6, BV15, and BV18 subfamilies showed no abnormal peaks. 3) TCR BV2 and BV17 yielded an abnormal peak in 3 HLA-B27-negative patients; however, no such abnormalities were detected in HLA-B27-positive patients. The abnormal expression of some TCR BV subfamilies in PBMCs from patients with uveitis may be associated with the immune pathogenesis of the disease. Our study provides the basis for further investigations into the pathogenesis of uveitis.

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Section: Discussionmentioning

confidence: 99%

Preliminary study of the clonal characteristics of the TCR BV subfamilies in T cells in the peripheral blood from patients with uveitis

Zou¹,

Yu²,

Zhang³

et al. 2014

Genet. Mol. Res.

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“…Therefore, the analysis of TCR use in cancer patients is an excellent tool for assessing tumor-specific immune responses [25]. RT-PCR GeneScan technology is one of the most sensitive methods for analyzing TCR use and clonal T cell expansion [12]. Using this method, preferential TCR use and clonal T cell expansions have been reported in patients with numerous infectious diseases [26,27], autoimmune diseases [11,28,29], and malignant tumors [30,31].…”

Section: Discussionmentioning

confidence: 99%

“…Many techniques have now been developed to analyze the complexity of the TCR repertoire [12][13][14]. In our previous study, skewed use of TCR V␤ subfamily T cells and oligoclonally expanded TCR V␤ subfamilies were detected in 29 cases with CML and 13 cases with B-cell ALL (B-ALL).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210BCR-ABL-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia

Zha¹,

Chen²,

Yang³

et al. 2011

Human Immunology

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“…The clinical trial data have already been published (6). Blood samples were taken at baseline and at the follow-up visits at weeks 2,4,8,12,16,24,32,40,48,52,60,68,76,84,92, 100, and 104. Subjects were classified into virological response (VR; n ϭ 12) or nonvirological response (NVR; n ϭ 8) groups, based on whether the serum HBV DNA level was less than 300 copies/ml at week 52.…”

Section: Methodsmentioning

confidence: 99%

“…When a clone of T cells expands after recognizing a peptide antigen, then the Gaussian distribution is disturbed. These disturbances are large enough to be detectable by the CDR3 size spectratyping technique (12), in which the entire repertoire of CDR3 regions associated with each V gene is PCR amplified with a labeled primer and size separated on a genetic analyzer that outputs the distribution of peak areas.…”

mentioning

confidence: 99%

Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8 ⁺ T Cells following Antiviral Treatment of Chronic Hepatitis B

Zhang

et al. 2011

Antimicrob Agents Chemother

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An increased CD8؉ T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8؉ T cells at these time points predict the virological response to therapy. Peripheral blood CD8؉ T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) ␤ chain variable region (V␤) gene family was analyzed, and the changes in the numbers of V␤ families with clonal expansions were compared in subjects with (n ‫؍‬ 12) and without (n ‫؍‬ Chronic hepatitis B (CHB) can lead to liver cirrhosis, liver failure, and liver cancer (10). CHB is always associated with replication of the hepatitis B virus (HBV) in the liver, and suppression of this replication by antiviral therapy leads to both cessation of disease activity and a decreased risk for the serious sequelae (11). Unfortunately, the suppression of viral replication induced by current antiviral therapies is not permanent in most patients, and life-long therapy is required to maintain disease inactivity. A therapeutic vaccine that permanently enhanced the patient's own immune response to the HBV would make a valuable contribution to the management of these patients.Long-term suppression of HBV replication in patients with an inactive, HBeAg-negative, chronic HBV infection is probably carried out by CD8 ϩ T cells responding to wild-type viral peptides presented by human leukocyte antigen (HLA) class I (13). Although CD8 ϩ T cells responding to peptides presented by the HLA-A*0201 allele have been widely studied, very little is known about the CD8 ϩ T cells that respond to peptides presented by other HLA class I alleles, which may be more relevant to the development of therapeutic vaccines in Asia. Boni et al. (4,5) identified an opportunity to study HBVspecific CD8 ϩ T cells from subjects with a wide range of HLA class I genotypes when they found a temporary increase in CD8 ϩ T cell responses to HBV peptides at 12 and 24 weeks after beginning antiviral therapy. Whether these responses influence the outcome of antiviral therapy is unknown. Thus, there is doubt as to whether they are genuine HBV-specific responses that might be useful targets of immunotherapy, or just HLA-and HBV-nonspecific responses resulting from TCR degeneracy (8).The complementarity-determining region 3 (CDR3) of the ␣ and ␤ polypeptides that make up the TCR are immediately 5Ј of the variable (V) sequences that distinguish the 24 families of ␤ chains and the 32 families of ␣ chains. The CDR3 regions are responsible for recognition of the antigenic peptides presented to the T cell by HLA class I. Consequently there needs to be a high level of diversity in these regions, which is generated by varying both the sequence and the number of amino acids. Variation in the number of amino ...

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Standardized analysis for the quantification of Vβ CDR3 T-cell receptor diversity

Cited by 29 publications

References 36 publications

Preliminary study of the clonal characteristics of the TCR BV subfamilies in T cells in the peripheral blood from patients with uveitis

Preliminary study of the clonal characteristics of the TCR BV subfamilies in T cells in the peripheral blood from patients with uveitis

Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210BCR-ABL-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia

Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8 ⁺ T Cells following Antiviral Treatment of Chronic Hepatitis B

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Standardized analysis for the quantification of Vβ CDR3 T-cell receptor diversity

Cited by 29 publications

References 36 publications

Preliminary study of the clonal characteristics of the TCR BV subfamilies in T cells in the peripheral blood from patients with uveitis

Preliminary study of the clonal characteristics of the TCR BV subfamilies in T cells in the peripheral blood from patients with uveitis

Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210BCR-ABL-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia

Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8 + T Cells following Antiviral Treatment of Chronic Hepatitis B

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Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8 ⁺ T Cells following Antiviral Treatment of Chronic Hepatitis B