TCRs with high affinity for foreign pMHC show self-reactivity

Phillip D. Holler, Lukasz K. Chlewicki, David M Kranz

Research output: Contribution to journalReview article

Abstract

T cells with high-affinity T cell receptors (TCRs) for a foreign peptide-major histocompatibility complex (pMHC) appear to be negatively selected, even though they have never seen the foreign antigen.To examine how this process operates, we used in vitro yeast display to isolate high-affinity TCRs from the T cell clone 2C. The TCRs showed fast on-rates, which were consistent with reduced CDR (complementarity determining region) flexibility, and cross-reactivity with other cognate pMHCs. T cell hybridomas transfected with a high-affinity TCR were stimulated by endogenous self-pMHC, which suggested that T cells bearing the TCR would be negatively selected. The immune system appears to maintain a repertoire of flexible, low-affinity TCRs at the expense of more effective high-affinity TCRs.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalNature Immunology
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2003

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T-Cell Antigen Receptor
Major Histocompatibility Complex
Peptides
T-Lymphocytes
Complementarity Determining Regions
Hybridomas
Immune System
Clone Cells
Yeasts
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

TCRs with high affinity for foreign pMHC show self-reactivity. / Holler, Phillip D.; Chlewicki, Lukasz K.; Kranz, David M.

In: Nature Immunology, Vol. 4, No. 1, 01.01.2003, p. 55-62.

Research output: Contribution to journalReview article

Holler, Phillip D. ; Chlewicki, Lukasz K. ; Kranz, David M. / TCRs with high affinity for foreign pMHC show self-reactivity. In: Nature Immunology. 2003 ; Vol. 4, No. 1. pp. 55-62.
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