Junctional region sequences of T-cell receptor β-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: Possible selection by cationic autoantigens

Sharlene Adams, Pierre Leblanc, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

We rescued from the spleens of 10 (SWR x NZB)F1 (SNF1) mice with lupus nephritis the T cells that were activated in vivo and cloned 268 T-cell lines and hybridomas. Only 12% of these T-cell clones had the functional ability to preferentially augment the production of pathogenic anti-DNA autoantibodies. Among these, 16 helper T-cell (T(h)-cell) clones that were mostly CD4+ and had the strongest autoantibody-inducing ability were analyzed for T-cell receptor (TCR) β-chain gene usage. Seven of the 16 T(h)-cell clones expressed β-chain variable region (V(β)) V(β)8 (8.2 or 8.3) genes and three expressed V(β)4, whereas two clones each used a V(β)1 or V(β)2 or V(β)14 gene, suggesting some restriction in TCR gene usage. Although heterogeneous, the V-D-J junctional region sequences of TCR β-chain genes used by these T(h)-cell clones invariably encoded one or more negatively charged residues (aspartic or glutamic acid) that had been generated in most cases by unspecified nucleotide (N) additions. Representative pathogenic autoantibody-inducing T(h)-cell clones could rapidly induce the development of lupus nephritis when injected into young prenephritic SNF1 mice. The pathogenic autoantibody-inducing T(h) cells expressing the anionic residues in their TCR β-chain junctions (complementarity-determining region CDR3) were probably selected by some cationic autoantigenic peptide presented by the anti-DNA B cells they preferentially helped. These results offer a clue regarding the nature of the primary autoantigen that may drive the pathogenic autoimmune response in lupus.

Original languageEnglish (US)
Pages (from-to)11271-11275
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number24
DOIs
StatePublished - 1991

Keywords

  • T-cell receptors
  • nephritogenic helper T cells
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • General

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