title: The central tolerance response to male antigen in normal mice is deletion and not receptor editing.
abstract: It is widely accepted that developing T cells can undergo clonal deletion in the thymus in response to a high affinity self-Ag. This is largely based on studies of TCR transgenics. However, encounter with high affinity self-Ag can also result in receptor editing in TCR transgenic models. Because all TCR transgenics display ectopic receptor expression, the tolerance mechanism that predominates in normal mice remains an open question. When self-Ag drives receptor editing during T cell development, one expects to find in-frame, self-reactive TCRalpha joins on TCR excision circles (TRECs), which are the products of secondary V/J recombination in the TCRalpha locus. Such joins are not expected if clonal deletion occurs, because the progenitor cell would be eliminated by apoptosis. To test the relative utilization of receptor editing vs clonal deletion, we determined the frequency of in-frame, male-specific joins on TRECs in male and female HYbeta transgenic mice. In comparison with female HYbeta transgenic mice, our analysis showed a lower frequency of TRECs with male-reactive V17J57 joins in male mice. Thus, it would appear that receptor editing is not a predominant tolerance mechanism for this self-Ag.
authors.affiliation: Department of Laboratory Medicine and Pathology and Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Philmore O
authors.initials: PO
authors.lastname: Holman
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Walsh
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
mesh_terms: D000818:Animals; D017637:Clonal Deletion / Q000235:genetics; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017393:RNA Editing / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000276:immunology
chemical_list: D006182:H-Y Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta