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

Medullary thymic epithelial cells (mTEC) are able to present soluble antigens 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). In addition, class Il heterodimers from mTEC migrated with apparently less relative 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 distinct migration profiles of class If heterodimers in both TEC types, class ii heterodimer-associated peptides were analyzed by matrix-assisted laser desorption 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 other hand, self peptides from two mTEC consisted predominantly of two CLIP variants with exceptional C-terminal extensions. C-terminally overhanging residues of CLIP in mTEC may be responsible for the distinct migration of class ii heterodimers in SDS-PAGE. Differences in migration of class II heterodimers on SDS gels was also observed in H2-DM+ vesicles isolated from both TEC. The possible contribution of self peptides bound to class II heterodimers in TEC to positive or negative selection of T cells in the thymus is discussed.