Identification of naturally processed peptides bound to the class I MHC molecule H-2Kd of normal and TAP-deficient cells.
This report details the biochemical features of natural peptides selected by the H-2Kd 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-2Kd (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 TAP-independent pathways selected for long peptides by class I MHC molecules.
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Anish
A
Suri
James J
JJ
Walters
Matteo G
MG
Levisetti
Michael L
ML
Gross
Emil R
ER
Unanue
D000596:Amino Acids / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology*; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology
D000596:Amino Acids; D000950:Antigens, Ly; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D010455:Peptides