A Broad Range of Self-Reactivity Drives Thymic Regulatory T Cell Selection to Limit Responses to Self

Hyang Mi Lee, Jhoanne L. Bautista, James Scott-Browne, James F. Mohan, Chyi Song Hsieh

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

The degree of T cell self-reactivity considered dangerous by the immune system, thereby requiring thymic selection processes to prevent autoimmunity, is unknown. Here, we analyzed a panel of T cell receptors (TCRs) with a broad range of reactivity to ovalbumin (OVA323-339) in the rat insulin promoter (RIP)-mOVA self-antigen model for their ability to trigger thymic self-tolerance mechanisms. Thymic regulatory T (Treg) cell generation in vivo was directly correlated with in vitro TCR reactivity to OVA-peptide in a broad ∼1,000-fold range. Interestingly, higher TCR affinity was associated with a larger Treg cell developmental "niche" size, even though the amount of antigen should remain constant. The TCR-reactivity threshold to elicit thymic negative selection and peripheral T cell responses was ∼100-fold higher than that of Treg cell differentiation. Thus, these data suggest that the broad range of self-reactivity that elicits thymic Treg cell generation is tuned to secure peripheral tolerance to self.

Original languageEnglish
Pages (from-to)475-486
Number of pages12
JournalImmunity
Volume37
Issue number3
DOIs
StatePublished - Sep 21 2012

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