Antigen-independent in vitro expansion of T cells does not affect the T cell receptor Vβ repertoire

Arenz, Monika; Herzog-Hauff, Sabine; Büschenfelde, K H Meyer zum; Löhr, Hanns

doi:10.1007/s001090050152

Cited by 14 publications

(11 citation statements)

References 15 publications

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“…We isolated CSF-infiltrating cells from a patient with relapsing-remitting MS during disease exacerbation and cloned them by limiting dilution with PHA as an unbiased stimulus [11]. Growing colonies were characterized for CD4/CD8 and TCRVβ expression, and clonality was confirmed by TCR-variable (TCR VB ) chain sequencing (Figure 1A and Table 1).…”

Section: Resultsmentioning

confidence: 99%

Recognition of Conserved Amino Acid Motifs of Common Viruses and Its Role in Autoimmunity

et al. 2005

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The triggers of autoimmune diseases such as multiple sclerosis (MS) remain elusive. Epidemiological studies suggest that common pathogens can exacerbate and also induce MS, but it has been difficult to pinpoint individual organisms. Here we demonstrate that in vivo clonally expanded CD4+ T cells isolated from the cerebrospinal fluid of a MS patient during disease exacerbation respond to a poly-arginine motif of the nonpathogenic and ubiquitous Torque Teno virus. These T cell clones also can be stimulated by arginine-enriched protein domains from other common viruses and recognize multiple autoantigens. Our data suggest that repeated infections with common pathogenic and even nonpathogenic viruses could expand T cells specific for conserved protein domains that are able to cross-react with tissue-derived and ubiquitous autoantigens.

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Section: Resultsmentioning

confidence: 99%

Recognition of Conserved Amino Acid Motifs of Common Viruses and Its Role in Autoimmunity

et al. 2005

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“…We decided to analyze promiscuous restriction in five TCCs (MN10, MN19, MN27, MN36, and MN47) generated from the CSF of an untreated HLA-DR2/DR13-positive RR-MS patient during disease exacerbation by limiting dilution and using PHA as an unbiased stimulus (33,34). Growing colonies were characterized for CD4/CD8 and TCR V␤ expression, and clonality was confirmed by TCR V␣ and ␤-chain sequencing (Fig.…”

Section: Promiscuous Hla Class II Restriction Of In Vivo-expanded Andmentioning

confidence: 99%

Redundancy in Antigen-Presenting Function of the HLA-DR and -DQ Molecules in the Multiple Sclerosis-Associated HLA-DR2 Haplotype

Sospedra

Muraro

Stefanová

et al. 2006

The Journal of Immunology

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The three HLA class II alleles of the DR2 haplotype, DRB1*1501, DRB5*0101, and DQB1*0602, are in strong linkage disequilibrium and confer most of the genetic risk to multiple sclerosis. Functional redundancy in Ag presentation by these class II molecules would allow recognition by a single TCR of identical peptides with the different restriction elements, facilitating T cell activation and providing one explanation how a disease-associated HLA haplotype could be linked to a CD4+ T cell-mediated autoimmune disease. Using combinatorial peptide libraries and B cell lines expressing single HLA-DR/DQ molecules, we show that two of five in vivo-expanded and likely disease-relevant, cross-reactive cerebrospinal fluid-infiltrating T cell clones use multiple disease-associated HLA class II molecules as restriction elements. One of these T cell clones recognizes >30 identical foreign and human peptides using all DR and DQ molecules of the multiple sclerosis-associated DR2 haplotype. A T cell signaling machinery tuned for efficient responses to weak ligands together with structural features of the TCR-HLA/peptide complex result in this promiscuous HLA class II restriction.

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“…In preceding experiments the chosen conditions of tissue culture and stimulation with mitogens did not alter the TCR BV repertoire (ref. 31 and authors' unpublished observations). Moreover, expansion of BV8 + T cells was seen exclusively in patients with chronic hepatitis C. Thus, simple skewing of the TCR repertoire by tissue culture and the stimulation process itself can be excluded.…”

Section: Discussionmentioning

confidence: 68%

Differential expansion of T‐cell receptor variable beta subsets after antigenic stimulation in patients with different outcomes of hepatitis C infection

Woitas¹,

Sippel²,

Althausen³

et al. 2002

Immunology

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Summary Persistent antigenic stimulation during chronic hepatitis C may alter the T‐cell receptor variable chain beta (TCR BV) repertoire as well as the cytokine responses of hepatitis C virus (HCV)‐specific T lymphocytes. We analysed the distribution of the TCR BV subsets 2.1, 3.1, 5.1, 6.1, 8, 13.1, 13.6, 14.1, 17.1, 21.3 in relation to intracytoplasmic expression of interleukin‐2, interferon‐γ, interleukin‐4 and interleukin‐10. Using flow cytometry, CD45RO+ memory T cells of 27 patients with chronic hepatitis C, eight patients with resolved HCV infection and 16 non‐HCV‐related controls were studied with and without stimulation by the HCV core, NS3, NS4, NS5a and NS5b proteins. Patients with chronic and resolved hepatitis C differed by larger basal TCR BV2.1+, BV6.1+, BV17.1+ and BV21.3+ subsets in chronic hepatitis C, which were correlated to the numbers of T cells with spontaneous interleukin‐2 and interferon‐γ production (r=0·51–0·73, P<0·05). Upon HCV‐specific stimulation these subsets did not expand, whereas a marked in vitro expansion of TCR BV8+ T cells in response to all HCV proteins was selectively noted in chronic hepatitis C (P<0·05). This expansion of TCR BV8+ memory T cells was significantly correlated to HCV‐induced interleukin‐10 expression (r=0·58–0·98, P<0·01). Thus, differential involvement of selected TCR BV subsets may be related to the outcome of HCV infection.

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Antigen-independent in vitro expansion of T cells does not affect the T cell receptor Vβ repertoire

Cited by 14 publications

References 15 publications

Recognition of Conserved Amino Acid Motifs of Common Viruses and Its Role in Autoimmunity

Recognition of Conserved Amino Acid Motifs of Common Viruses and Its Role in Autoimmunity

Redundancy in Antigen-Presenting Function of the HLA-DR and -DQ Molecules in the Multiple Sclerosis-Associated HLA-DR2 Haplotype

Differential expansion of T‐cell receptor variable beta subsets after antigenic stimulation in patients with different outcomes of hepatitis C infection

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