Shared Human T Cell Receptor V _β Usage to Immunodominant Regions of Myelin Basic Protein

Abstract

Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.

Structural Analysis of TCRα and β Chains from Human T‐Cell Clones Specific for Small Nuclear Ribonucleoprotein Polypeptides Sm‐D, Sm‐B and U1–70 kDa: TCR Complementarity Determining Region 3 Usage Appears Highly Conserved

“…Only a few reports have looked at the usage of TCR among antigen specific T-cell clones in human autoimmunity. Wucherpfennig et al [3] was the first to report an increase in the use of several V regions among myelin basic protein specific T-cell clones isolated from patients. Furthermore, Desai-Mehta et al [4] found that although the a and b V region usage was variable among T-cells lines which induced the production of anti-DNA autoantibodies, there was a trend for common motifs among the CDR3.…”

Limited heterogeneity of biased T‐cell receptor Vβ gene usage in lung but not blood T cells in active pulmonary sarcoidosis

“…[7][8][9][10][11][12][13][14] This approach is based on the knowledge that antigen-specific immune responses can be associated with biases in the usage of specific -chain are seen in antigen-specific T cells specific for cytochrome-c, myelin basic protein, mycobacterial heat shock proteins, influenza virus and tetanus toxoid. [15][16][17][18][19][20][21] Biases in the usage of Va TCR gene segments have also been reported for selected antigen-specific T cells. 22 In these instances, components of the a -or b -chain of the TCR appear to be selected by limited antigenic peptides complexed with MHC class II molecules.…”

In Vivo Maintenance of Human Regulatory T Cells during CD25 Blockade

“…Daclizumab, a humanized Ab that binds CD25 and blocks its interaction with IL-2 (14), is currently in clinical development for relapsing-remitting multiple sclerosis (RRMS), a T cell-mediated neuroinflammatory disorder (15)(16)(17). Results from a 600-patient, randomized, double-blinded, placebo-controlled trial demonstrated that daclizumab has robust clinical efficacy (18).…”