CLIP-derived self peptides bound to MHC class II molecules of medullary thymic epithelial cells differ from those of cortical thymic epithelial cellsin their diversity, length, and C-terminal processing

Medullary thymic epithelial cells (mTEC) are able to present soluble antige ns to CD4(+) helper T cell lines, whereas cortical thymic epithelial cells (cTEC) are not (Mizuochi, T., et al., J. Exp. Med. 1992. 175: 1601-1605). I n addition, class Il heterodimers from mTEC migrated with apparently less r elative molecular mass in SDS-PAGE than those from cTEC (Kasai; M. et al., Eur. J. Immunol. 1998. 28:1867-1876). To investigate the cause of the disti nct migration profiles of class If heterodimers in both TEC types, class ii heterodimer-associated peptides were analyzed by matrix-assisted laser des orption ionization mass spectrometry. Self peptides from cTEC were shown to vary moderately in length and to be highly diverse, including low amounts of CLIP (class Ii-associated invariant chain peptide) variants. On the othe r hand, self peptides from two mTEC consisted predominantly of two CLIP var iants with exceptional C-terminal extensions. C-terminally overhanging resi dues of CLIP in mTEC may be responsible for the distinct migration of class ii heterodimers in SDS-PAGE. Differences in migration of class II heterodi mers on SDS gels was also observed in H2-DM+ vesicles isolated from both TE C. The possible contribution of self peptides bound to class II heterodimer s in TEC to positive or negative selection of T cells in the thymus is disc ussed.