Incomplete TCR-β allelic exclusion accelerates spontaneous autoimmune arthritis in K/BxN TCR transgenic mice.
Allelic exclusion of antigen receptor loci is a fundamental mechanism of immunological self-tolerance. Incomplete allelic exclusion leads to dual T-cell receptor (TCR) expression and can allow developing autoreactive αβ T lymphocytes to escape clonal deletion. Because allelic exclusion at the TCR-β locus is more stringent than at the TCR-α locus, dual TCR-β expression has not been considered a likely contributor to autoimmunity. We show here that incomplete TCR-β allelic exclusion permits developing thymocytes bearing the autoreactive, transgene-encoded KRN TCR to be positively selected more efficiently, thereby accelerating the onset of spontaneous autoimmune arthritis. Our findings highlight dual TCR-β expression as a mechanism that can enhance the maturation of autoreactive pathogenic T cells and lead to more rapid development of autoimmune disease.
Center for Immunology and Department of Pediatrics, University of Minnesota, Minneapolis, MN 55414, USA.
Jennifer L
JL
Auger
Stefanie
S
Haasken
Elizabeth M
EM
Steinert
Bryce A
BA
Binstadt
D000483:Alleles; D000818:Animals; D001168:Arthritis / Q000235:genetics* / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009205:Myocarditis / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D060168:Thymocytes / Q000276:immunology; D019076:Transgenes
D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta