Abstract
A transcription profiling study, together with genetic linkage data, provides a molecular map of the T-cell negative selection response in vivo.
Highlights
T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self
Immunological self-tolerance depends upon negative selection in the thymus, whereby T cells bearing T cell receptors (TCRs) with high avidity for self peptide-major histocompatibility complex (MHC) complexes are purged from the developing repertoire before they become functionally active in the periphery [1]
A measure of TCR signaling is required for thymocytes to mature from DP into single positive (SP) cells, an opposite process requiring a weak avidity for self peptideMHC in order to initiate the changes of cell survival and maturation referred to as positive selection
Summary
We use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip, Smox, Pdrg, Id1, Pdcd, Ly6c, Pdia, Trim and Trim
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
