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High affinity interactions promote T regulatory positive selection in the thymus
Author(s) -
Haymaker Cara L.,
Divekar Rohit,
Cascio Jason,
Yu Ping,
Zaghouani Habib
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.843.2
Subject(s) - negative selection , biology , positive selection , effector , immunology , selection (genetic algorithm) , clonal deletion , t cell receptor , chimera (genetics) , gene , immune system , genetics , t cell , genome , artificial intelligence , computer science
Many autoimmune disorders have been linked to a lack in T regulatory cells. As such, an understanding of how these cells develop and mature is critical. While thymic selection of effector T cells has been described, this process remains largely undefined for Tregs. Since only the DM20 form of proteolipid protein (PLP) is expressed in the thymus during fetal and neonatal life, thymic selection against PLP139‐151, which is missing in DM20 is not operative during those periods. PLP139‐151 (designated PLP 1 ) as well as PLP 1 derived altered peptides with degenerate affinity to PLP 1 ‐specific TCR were expressed on immunoglobulin (Ig) and the resulting chimeras were used to cross the maternal placenta, deliver the peptides from mother to fetus, and restore peptide selection during the fetal and neonatal period. This model was then used to determine whether Tregs are subject to thymic selection and to gauge the affinity required for such selection. The findings indicate that high affinity interactions promote the positive selection of Tregs. Indeed, Ig chimeras harboring high avidity peptides facilitated the positive selection of Tregs resulting in a higher number of Tregs progressing past the double positive stage in the thymus. However, chimeras incorporating low affinity peptide did not drive positive selection of Tregs in the thymus. Research supported by NIH grant NS37406.