NATURALLY PROCESSED CYTOKINE-DERIVED PEPTIDE BOUND TO HLA-CLASS-II MOLECULES

Sequence analysis of HLA-class II (HLA-DRbeta1-1502 and 1104)-bound se lf-peptides from a transformed B cell line was performed. The sequence s of naturally processed self-peptides bound to HLA-DR2 and DR5 were c ompared with protein and nucleic acid data bases for homology to known precursor proteins. Of the matches to known precursors, one peptide s howed 100% homology to the third framework and CDR3 regions of Ig V(H) expressed by the line. Another peptide matched 100% to the human equi valent of macrophage inflammatory protein (MIP). A synthetic peptide c orresponding to the naturally processed form of MIP (KPGVIFLTKRSRQV) w as shown to inhibit Ag-specific HLA-DRbeta11104-restricted T cell pro liferation. This indicates that the MIP peptide binds to HLA-DRbeta11 104. The MIP peptide belongs to a set of peptides that showed uniform NH2-terminal processing. In this set, proline always occurred as the s econd residue followed by a basic lysine or argininine in position nin e. This suggests that final NH2-terminal processing of peptides preced es their binding to MHC molecules. A distinct, second set of peptides showed ragged NH2-terminii, as has been reported for other naturally p rocessed MHC-class II-bound self-peptides.