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Research Article Free access | 10.1172/JCI117695

Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibody-inducing T cells in human lupus.

A Desai-Mehta, C Mao, S Rajagopalan, T Robinson, and S K Datta

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.

Find articles by Desai-Mehta, A. in: PubMed | Google Scholar

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.

Find articles by Mao, C. in: PubMed | Google Scholar

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.

Find articles by Rajagopalan, S. in: PubMed | Google Scholar

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.

Find articles by Robinson, T. in: PubMed | Google Scholar

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.

Find articles by Datta, S. in: PubMed | Google Scholar

Published February 1, 1995 - More info

Published in Volume 95, Issue 2 on February 1, 1995
J Clin Invest. 1995;95(2):531–541. https://doi.org/10.1172/JCI117695.
© 1995 The American Society for Clinical Investigation
Published February 1, 1995 - Version history
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Abstract

The production of potentially pathogenic anti-DNA autoantibodies in SLE is driven by special, autoimmune T helper (Th) cells. Herein, we sequenced the T cell receptor (TCR) alpha and beta chain genes expressed by 42 autoimmune Th lines from lupus patients that were mostly CD4+ and represented the strongest inducers of such autoantibodies. These autoimmune TCRs displayed a recurrent motif of highly charged residues in their CDR3 loops that were contributed by N-nucleotide additions and also positioned there by the recombination process. Furthermore, Th lines from four of the five patients showed a marked increase in the usage of the V alpha 8 gene family. Several independent Th lines expressed identical TCR alpha and/or beta chain sequences indicating again antigenic selection. 10 of these Th lines could be tested further for antigenic specificity. 4 of the 10 pathogenic anti-DNA autoantibody-inducing Th lines responded to the non-histone chromosomal protein HMG and two responded to nucleosomal histone proteins; all presented by HLA-DR molecules. Another Th line responded to purified DNA more than nucleosomes. Thus, these autoimmune Th cells of lupus patients respond to charged epitopes in various DNA-binding nucleoproteins that are probably processed and presented by the anti-DNA B cells they selectively help.

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