Cutting edge: Highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease

Gerald P. Morris, Paul M. Allen

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Alloreactivity is the response of T cells to MHC molecules not encountered during thymic development. A small population (1-8%) of peripheral T cells in mice and humans express two TCRs due to incomplete allelic exclusion of TCRα, and we hypothesized they are highly alloreactive. FACS analysis of mouse T cell MLR revealed increased dual TCR T cells among alloreactive cells. Quantitative assessment of the alloreactive repertoire demonstrated a nearly 50% reduction in alloreactive T cell frequency among T cells incapable of expressing a secondary TCR. We directly demonstrated expansion of the alloreactive T cell repertoire at the single cell level by identifying a dual TCR T cell with distinct alloreactivities for each TCR. The importance of dual TCR T cells is clearly demonstrated in a parent-into-F1 model of graft-vs-host disease, where dual TCR T cells comprised up to 60% of peripheral activated T cells, demonstrating a disproportionate contribution to disease.

Original languageEnglish
Pages (from-to)6639-6643
Number of pages5
JournalJournal of Immunology
Volume182
Issue number11
DOIs
StatePublished - Jun 1 2009

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