{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

Lecture 11-Lymphocyte development II

Lecture 11-Lymphocyte development II - Dueling repressors...

Info icon This preview shows pages 1–4. Sign up to view the full content.

View Full Document Right Arrow Icon
1 “Dueling repressors” Runx3 and Thpok at the heart of the CD4/CD8 lineage choice Lie Wang, Rémy Bosselut. Journal of Immunology, 2009, 183: 2903 2910 Possible basis for TCR signal strength input to bias CD4/CD8 lineage decision network Rothenberg, 2009 Immunol. Cell Biol. 87(2):109-12. Positive and negative selection: problems faced by T and B cells Both T and B cells generate receptors with random specificities Both run the risk of autoreactive receptors in repertoire Positive feedback inherent in immune responses could create overwhelming autoimmunity Initial repertoire purging… nice idea, but how? Problems of repertoire selection, continued TCR and Ig repertoires are selected before cells go to periphery Random nature of VDJ rearrangement + allelic exclusion means lots of cells with failed or autoreactive receptors Selection needed in favor of cells with some receptor (no receptor death) Selection needed to remove many/most cells with highly self-reactive receptors
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
2 Positive vs. negative selection: what is the choice that the cells have to make? T cell case is easier to study because +, - selection occur in different thymic domains Signal strength distinguishing positive from negative selection Building an assay system for TCR-ag recognition in development: Positive selection of CD8 + cells in OT-1 TCR-tg thymus is blocked by lack of surface MHC cl. I Hogquist et al. 1994 b 2m is common, soluble chain required for membrane stabilization of all MHC cl. I structures… single-gene knockout blocks almost all cl. I MHC surface expression Optimal OT-1 target antigen peptide addback causes deletion in fetal thymus organ culture, though potency is less without b 2 m Hogquist et al. 1994
Image of page 2