Cutting edge: Highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease.
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 TCRalpha, 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-F(1) 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.
Morris
Gerald P
GP
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Allen
Paul M
PM
D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell