Identification of naturally processed peptides bound to the class I MHC molecule H‐2K^d of normal and TAP‐deficient cells

Abstract

This report details the biochemical features of natural peptides selected by the H-2K d class I MHC molecule. In normal cell lines, the length of the naturally processed peptides ranged from 8 to 18 amino acids, although the majority were 9-mers (16% were longer than nine residues). The binding motif for the 9-mer peptides was dominated by the presence of a tyrosine at P2 and an isoleucine/leucine at the P9 position. The P2 residue contributed most towards binding; and the short peptides bound better and formed longer-lived cell surface complexes than the long peptides, which bound poorly and dissociated rapidly. The longer peptides did not exhibit this strictly defined motif. Trimming the long peptides to their shorter forms did not enhance binding and conversely, extending the 9-mer peptides did not decrease binding. The long peptides were present on the cell-surface bound to H-2K d (Kd) and were not intermediate products of the class I MHC processing pathway. Finally, in two different TAP-deficient cells the long peptides were the dominant species, which suggested that TAPindependent pathways selected for long peptides by class I MHC molecules.

Structural Definition of the H-2Kd Peptide-binding Motif

“…5) (60) and further available in MHC peptide databases (51)(52)(53). Although peptides of alternate length have been shown to associate with K d , the resulting complexes are short-lived and are unlikely to be physiologically dominant (60).…”

“…The sequences of a number of naturally processed peptides that are presented by K d have been identified, including self-peptides (12,(15)(16)(17)(18)(19)(20)(21)60) and those encoded by viruses (14,22,23), parasites (24,25), and bacteria (26). The first virally encoded T-cell epitope ever described was in fact a K d -binding peptide derived from influenza A/PR/8/34 nucleoprotein (27).…”

Detection of vasostatin-1-specific CD8+ T cells in non-obese diabetic mice that contribute to diabetes pathogenesis

“…1 T cells in the context of H2-K d in NOD mice [23]. These preferred amino acids at P2 and P9 are Y and L, respectively [23].…”

“…These preferred amino acids at P2 and P9 are Y and L, respectively [23]. We analysed all potential 9-mer peptide sequences from vasostatin-1 with SYFPEITHI epitope prediction software [24].…”

Generation of MHC class I ligands in the secretory and vesicular pathways

“…Ligands from three classical MHC class I molecules, K d , HLA-A2 and HLA-B51, and from one class I-like molecule, Qa-1 b , were recently analyzed [42][43][44]. Unexpectedly, no common picture emerges from these reports.…”