Specificity and T cell receptor β chain usage of a human collagen type II-reactive T cell clone derived from a healthy individual

The T cell receptor (TCR)-alpha/beta CD4-8- (double negative, DN) T cell subset is characterized by an oligoclonal repertoire and a restricted V gene usage. By immunizing mice with a DN T cell clone we generated two monoclonal antibodies (mAbs) against V alpha 24 and V beta 11, which have been reported to be preferentially expressed in DN T cells. Using these antibodies, we could investigate the expression and pairing of these V alpha and V beta gene products among different T cell subsets. V alpha 24 is rarely expressed among CD4+ and especially CD8+ T cells. In these cases it is rearranged to different J alpha segments, carries N nucleotides, and pairs with different V beta. Remarkably, V alpha 24 is frequently expressed among DN T cells and is always present as an invariant rearrangement with J alpha Q, without N region diversity. This invariant V alpha 24 chain is always paired to V beta 11. This unique V alpha 24-J alpha Q/V beta 11 TCR was found in expanded DN clones from all the individuals tested. These findings suggest that the frequent occurrence of cells carrying this invariant TCR is due to peripheral expansion of rare clones after recognition of a nonpolymorphic ligand.

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Pathologic clonal cytotoxic T-cell responses: nonrandom nature of the T-cell–receptor restriction in large granular lymphocyte leukemia

Blood ◽

10.1182/blood-2004-10-4045 ◽

2005 ◽

Vol 106 (8) ◽

pp. 2769-2780 ◽

Cited By ~ 75

Author(s):

Marcin W. Wlodarski ◽

Christine O'Keefe ◽

Evan C. Howe ◽

Antonio M. Risitano ◽

Alexander Rodriguez ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Cell Clone ◽

Clonal Selection ◽

Cell Receptor ◽

Large Granular Lymphocyte ◽

Molecular Signature ◽

Autoimmune Response ◽

Cytotoxic T Cell ◽

T Cell Clone

AbstractT-cell large granular lymphocyte (T-LGL) leukemia is a clonal lymphoproliferation of cytotoxic T cells (CTLs) associated with cytopenias. T-LGL proliferation seems to be triggered/sustained by antigenic drive; it is likely that hematopoietic progenitors are the targets in this process. The antigen-specific portion of the T-cell receptor (TCR), the variable beta (VB)–chain complementarity-determining region 3 (CDR3), can serve as a molecular signature (clonotype) of a T-cell clone. We hypothesized that clonal CTL proliferation develops not randomly but in the context of an autoimmune response. We identified the clonotypic sequence of T-LGL clones in 60 patients, including 56 with known T-LGL and 4 with unspecified neutropenia. Our method also allowed for the measurement of clonal frequencies; a decrease in or loss of the pathogenic clonotype and restoration of the TCR repertoire was found after hematologic remission. We identified 2 patients with identical immunodominant CDR3 sequence. Moreover, we found similarity between multiple immunodominant clonotypes and codominant as well as a nonexpanded, “supporting” clonotypes. The data suggest a nonrandom clonal selection in T-LGL, possibly driven by a common antigen. In contrast, the physiologic clonal CTL repertoire is highly diverse and we were not able to detect any significant clonal sharing in 26 healthy controls.

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Diverse patterns of unresponsiveness in an acetylcholine receptor-specific T-cell clone from a myasthenia gravis patient after engaging the T-cell receptor with three different ligands

Journal of Neuroimmunology ◽

10.1016/s0165-5728(97)00202-6 ◽

1998 ◽

Vol 82 (2) ◽

pp. 182-190 ◽

Cited By ~ 9

Author(s):

Alison P Bond ◽

Louise Corlett ◽

S.John Curnow ◽

Edward Spack ◽

Nick Willcox ◽

...

Keyword(s):

T Cell ◽

Myasthenia Gravis ◽

Acetylcholine Receptor ◽

T Cell Receptor ◽

Cell Clone ◽

Cell Receptor ◽

T Cell Clone

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Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

Journal of Experimental Medicine ◽

10.1084/jem.184.5.1755 ◽

1996 ◽

Vol 184 (5) ◽

pp. 1755-1768 ◽

Cited By ~ 5

Author(s):

U McKeever ◽

S Khandekar ◽

J Newcomb ◽

J Naylor ◽

P Gregory ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Adoptive Transfer ◽

Cell Clone ◽

Nod Mice ◽

Cell Receptor ◽

Transfer Model ◽

Maternal Immunization ◽

Nonobese Diabetic ◽

T Cell Clone

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

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