Naturally processed cytokine-derived peptide bound to HLA-class II molecules.
Sequence analysis of HLA-class II (HLA-DR beta 1-1502 and 1104)-bound self-peptides from a transformed B cell line was performed. The sequences of naturally processed self-peptides bound to HLA-DR2 and DR5 were compared with protein and nucleic acid data bases for homology to known precursor proteins. Of the matches to known precursors, one peptide showed 100% homology to the third framework and CDR3 regions of Ig VH expressed by the line. Another peptide matched 100% to the human equivalent of macrophage inflammatory protein (MIP). A synthetic peptide corresponding to the naturally processed form of MIP (KPGVIFLTKRSRQV) was shown to inhibit Ag-specific HLA-DR beta 1*1104-restricted T cell proliferation. This indicates that the MIP peptide binds to HLA-DR beta 1*1104. The MIP peptide belongs to a set of peptides that showed uniform NH2-terminal processing. In this set, proline always occurred as the second residue followed by a basic lysine or arginine in position nine. This suggests that final NH2-terminal processing of peptides precedes their binding to MHC molecules. A distinct, second set of peptides showed ragged NH2-terminii, as has been reported for other naturally processed MHC-class II-bound self-peptides.
Harris
P E
PE
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York, NY 10032.
Maffei
A
A
Liu
Z
Z
Colovai
I
I
Reed
E F
EF
Inghirami
G
G
Suciu-Foca
N
N
D000595:Amino Acid Sequence; D001483:Base Sequence; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism*; D015802:HLA-DR2 Antigen / Q000378:metabolism*; D015805:HLA-DR5 Antigen / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D015802:HLA-DR2 Antigen; D015805:HLA-DR5 Antigen; D010455:Peptides