Comparative sequence analysis of the human T cell receptor ? chain in juvenile rheumatoid arthritis and juvenile spondylarthropathies: Evidence for antigenic selection of T cells in the synovium

ABSTRACT Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8+ T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vβ CDR3 region of clonally expanded CD8+ T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.

Download Full-text

The ht beta gene encodes a novel CACCC box-binding protein that regulates T-cell receptor gene expression

Molecular and Cellular Biology ◽

10.1128/mcb.13.9.5691-5701.1993 ◽

1993 ◽

Vol 13 (9) ◽

pp. 5691-5701

Author(s):

Y Wang ◽

J A Kobori ◽

L Hood

Keyword(s):

Gene Expression ◽

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Binding Protein ◽

Cell Receptor ◽

Regulatory Function ◽

Human T Cell ◽

Alpha Gene ◽

Beta Gene

A gene encoding a novel CACCC box-binding protein that binds to the promoter region of the human T-cell receptor (TCR) V beta 8.1 gene and the mouse TCR alpha gene silencer has been cloned. This gene, termed ht beta, contains four zinc fingers of the class Cys2-X12-His2 that may be responsible for DNA binding and a highly negatively charged region that defines a putative transcriptional activation domain. Analysis of the expression of ht beta mRNA revealed similar expression levels and patterns in various cell lines. The bacterially expressed ht beta protein can bind to the CACCC box in both the human TCR V beta 8.1 gene promoter and the mouse TCR alpha gene silencer. The CACCC box is essential for efficient transcription of the V beta 8.1 promoter. Cotransfection with an ht beta expression plasmid and a reporter vector indicated that ht beta can activate human TCR V beta 8.1 gene transcription. ht beta also is able to counteract the silencing effect of the mouse TCR alpha gene silencer. The CACCC box has been found in almost all V beta 8.1 gene subfamily members and in both TCR alpha and beta gene enhancers in humans and mice. These results suggest that the CACCC box-binding protein may have an important regulatory function for TCR gene expression in alpha beta T cells versus gamma delta T cells.

Download Full-text

Sequence analysis of bovine T-cell receptor ? chain

Immunogenetics ◽

10.1007/bf00702490 ◽

1990 ◽

Vol 31 (1) ◽

pp. 57-60 ◽

Cited By ~ 17

Author(s):

Naotaka Ishiguro ◽

Astuko Tanaka ◽

Morikazu Shinagawa

Keyword(s):

T Cell ◽

Sequence Analysis ◽

T Cell Receptor ◽

Cell Receptor ◽

Receptor Chain

Download Full-text

A Kinetic Threshold between Negative and Positive Selection Based on the Longevity of the T Cell Receptor–Ligand Complex

Journal of Experimental Medicine ◽

10.1084/jem.189.10.1531 ◽

1999 ◽

Vol 189 (10) ◽

pp. 1531-1544 ◽

Cited By ~ 92

Author(s):

Calvin B. Williams ◽

Deborah L. Engle ◽

Gilbert J. Kersh ◽

J. Michael White ◽

Paul M. Allen

Keyword(s):

T Cells ◽

T Cell ◽

Positive Selection ◽

T Cell Receptor ◽

Cell Receptor ◽

Ligand Complex ◽

Altered Peptide Ligands ◽

Self Peptides ◽

Selection Of

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II– restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64–76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR–ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR–ligand complexes.

Download Full-text