Mitochondria as a sequestration site for incomplete TCRß peptides: the TCRß transmembrane domain is a sufficient mitochondrial targeting signal.

ABSTRACT

The existence of incomplete T cell receptor (TCR) mRNA forms, including germline transcripts and products of unfruitful TCR rearrangements, has long been known. However, it is unclear whether these molecules are functional. We have previously shown that T cells also contain truncated TCRß peptides that lack the N-terminal part and contain C-terminus sequences. These partial forms of TCRß, target the mitochondrion and induce apoptosis, exhibiting a novel mode of TCR mediated cell death. Here we aimed at analyzing the minimal TCR sequences that direct the peptide to the mitochondrion. It is shown that truncated TCRß, targets mitochondria and induces mitochondrial perinuclear clustering, in both monkey COS-7 and human 293 cells. These phenomena are mediated by the C-terminus of the molecule. Whereas the positively charged amino acids flanking the transmembrane domain (TMD) of TCRß are beneficial for this process, they are not essential. Indeed, the isolated TMD of TCRß serves as a sufficient mitochondrial targeting sequence. These results indicate that any given partial form of TCRß, that contains the TMD, is bound to be sequestered by the mitochondrion. This may assure that incomplete TCR forms would not interfere with correct TCR complex formation.