24 research outputs found
alphabeta T cell receptors as predictors of health and disease
The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR \u27signatures\u27 raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome
Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells
Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.Octapharma research funding; Fundação para a Ciência e a Tecnologia postdoctoral fellowships: (SFRH/BPD/20806/2004, SFRH/BPD/34648/2007); FCT Programa Pessoa travel grant
Polymorphism in a T-cell receptor variable gene is associated with susceptibility to a juvenile rheumatoid arthritis subset
This report demonstrates a T-cell receptor (Tcr) restriction fragment length polymorphism, defined by a Tcrb-V6.1 gene probe and Bgl II restriction enzyme, to be absolutely correlated with allelic variation in the coding sequence of a Tcrb-V6.1 gene. A pair of non-conservative amino acid substitutions distinguish the Tcrb-V6.1 allelic variants. An association of this Tcrb-V6.1 gene allelic variant with one form of juvenile rheumatoid arthritis (JRA) was established in a cohort of 126 patients. The association was observed in patients possessing the HLA-DQA1*0101 gene. Among HLA-DQA*0101 individuals, 19 of 26 patients (73.1%) carried one particular Tcrb-V6.1 gene allele as opposed to 11 of 33 controls (33%; p<0.005). Haplotypes carrying this HLA gene have previously been shown to confer increased risk for progression of arthritis in JRA. This demonstration of a disease-associated Tcrb-V gene allelic variant has not, to our knowledge, been previously reported and supports the contribution of polymorphism in the Tcr variable region genomic repertoire to human autoimmune disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46750/1/251_2004_Article_BF00166831.pd
Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells
V beta -specific activation of T cells by the HIV glycoprotein gp160
Studies by several groups have suggested that HIV infection in vivo results in a V beta -specific alteration of the TCR repertoire and that this might play a role in the pathogenesis of AIDS. However, there is very little agreement as to which V beta segments are affected. In order to circumvent the confounding factors present in vivo we have examined the abilities of both a crude protein extract of HIV and purified gp160 to alter the V beta repertoire of normal T cells in vitro. We find that both a crude extract of HIV as well as gp160 specifically activate T cells expressing a common set of V beta segments (V beta 3, 12, 14, 15, and sometimes V beta 17 and 20) in individuals of disparate HLA type. This set of V beta segments is remarkably similar to those recognized by staphlococcal enterotoxin B and supports the hypothesis that bacterial superantigens produced by opportunistically acquired micro-organisms could have an exacerbating effect in AIDS
Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.
Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)
Scid mice develop a severe, chronic, and lethal IBD 3–6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft [7]. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-2-positive CD4+ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4+ T cells which stained positive for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8–14-fold increase in splenic G/M-CFC compared with control mice. No significant difference in the number of G/M-CFC per total spleen was found between non-transplanted and disease scid mice, although both groups of mice showed a nearly two-fold increase compared with control mice. G/M-CFC were never found in the thymus, liver or lymph nodes of diseased mice. Immunohistochemistry revealed that the multinucleated giant cells observed in the gut wall of diseased mice did not represent haematopoietic foci, but were derived from macrophages. These observations point towards a dominant role for Th1-type CD4+ T cells in the immunopathogenesis of IBD, whereas haematopoiesis does not seem to be affected by the development of the disease