T Cell Receptor Cross-Reactivity between Similar Foreign and Self Peptides Influences Naive Cell Population Size and Autoimmunity

Ryan W. Nelson, Daniel Beisang, Noah J. Tubo, Thamotharampillai Dileepan, Darin L. Wiesner, Kirsten Nielsen, Marcel Wüthrich, Bruce S. Klein, Dmitri I. Kotov, Justin A. Spanier, Brian T. Fife, James J. Moon, Marc K. Jenkins

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

T cell receptor (TCR) cross-reactivity between major histocompatibility complex II (MHCII)-binding self and foreign peptides could influence the naive CD4+ Tcell repertoire and autoimmunity. We found that nonamer peptides that bind to the same MHCII molecule only need to share five amino acids to cross-react on the same TCR. This property was biologically relevant because systemic expression of a self peptide reduced the size of a naive cell population specific for a related foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an incompletely deleted naive Tcell population specific for a tissue-restricted self peptide could be triggered by related microbial peptides to cause autoimmunity. Thus, TCR cross-reactivity between similar self and foreign peptides can reduce the size of certain foreign peptide-specific Tcell populations and might allow Tcell populations specific for tissue-restricted self peptides to cause autoimmunity after infection.

Original languageEnglish (US)
Pages (from-to)95-107
Number of pages13
JournalImmunity
Volume42
Issue number1
DOIs
StatePublished - Jan 20 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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