Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity.

The SET and domain 1 () locus encodes three tissue-restricted isoforms. Two previously characterized isoforms, and are heart and skeletal muscle-restricted histone methyl transferases. Here we report that a third, non-catalytic isoform, is expressed predominantly in activated CD8 T cells. While deficient CD8 T cells undergo activation-induced apoptosis, neither of two classical mechanisms activation-induced cell death nor activated cell autonomous death are utilized. Instead, accumulates within both mitochondria and the immunological synapse where it associates with Bcl-2, FK506-Binding Protein 8/38 (FKBP38) and Calcineurin. This complex maintains Bcl-2 phosphorylation, enhanced mitochondrial localization, and restricted apoptosis of activated CD8 T cells. We suggest that CD8 T cell death is governed, in part, by regulation of Bcl2-mediated restriction of outer mitochondrial membrane integrity.