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Molecular interactions between transfected human TCR, immunodominant myelin basic protein peptide 152-165, and HLA-DR13.

A E Hastings, C K Hurley, E D Robinson, K Salerno, E Hernandez and J R Richert
J Immunol October 15, 1996, 157 (8) 3460-3471;
A E Hastings
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C K Hurley
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E D Robinson
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K Salerno
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E Hernandez
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J R Richert
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Abstract

Chimeric TCR transfectants expressing human extracellular sequences and murine intracellular/transmembrane sequences were generated to analyze the trimolecular interaction between myelin basic protein (MBP) autoantigen, HLA, and a TCR isolated from a patient with multiple sclerosis. Chimeric transfectants responded to TCR activation by CD3- and TCRBV22S1-specific mAbs and by superantigen. Additionally, chimeric transfectants responded to autoantigen-specific activation with MBP 152-165 when presented by DR(alpha,beta1*1301) independent of the CD4 adhesion molecule. Transfectants did not respond to Ag presented by other HLA-DR molecules, including the closely related DR(alpha,beta1*1302). In peptide-binding studies with a panel of serial alanine-substituted MBP peptides, HLA contact residues necessary for anchoring MBP 152-165 to DR(alpha,beta1*1301) were also defined: 154 (F), 159 (R), and 162 (R). The chimeric TCR transfectant's differential response to a similar panel of MBP analogues defined residues that interact with the TCR: 153 (I), 155 (K), 156 (L), 160 (D), and 161 (S). Analysis of molecular interactions, such as those described in this work, may be central to developing new strategies for suppressing Ag-specific responses in human autoimmune disease.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 8
15 Oct 1996
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Molecular interactions between transfected human TCR, immunodominant myelin basic protein peptide 152-165, and HLA-DR13.
A E Hastings, C K Hurley, E D Robinson, K Salerno, E Hernandez, J R Richert
The Journal of Immunology October 15, 1996, 157 (8) 3460-3471;

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Molecular interactions between transfected human TCR, immunodominant myelin basic protein peptide 152-165, and HLA-DR13.
A E Hastings, C K Hurley, E D Robinson, K Salerno, E Hernandez, J R Richert
The Journal of Immunology October 15, 1996, 157 (8) 3460-3471;
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Print ISSN 0022-1767        Online ISSN 1550-6606