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 II 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 II 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.
Kasai
M
M
Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Tokyo, Japan. kasai@nih.go.jp
Kropshofer
H
H
Vogt
A B
AB
Kominami
E
E
Mizuochi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain