Presentation of endogenous peptide/MHC class I complexes is profoundly influenced by specific C-terminal flanking residues

N. Shastri, T. Serwold, F. Gonzalez

Research output: Contribution to journalArticle

Abstract

Processing of intracellular proteins yields 8-11 residue peptides that are displayed on the APC surface as peptide/MHC class I complexes. The remarkably precise excision of antigenic peptides from their precursor polypeptides raises the question of whether specific flanking residues influence presentation efficiency. Here we addressed this question by analyzing the generation of OVA/Kb or influenza nucleoprotein/Db complexes in APC expressing precursors with varying N- or C-terminal flanking residues. We find that T cell responses were not significantly affected by varying the N- terminal flanking residue in the precursors. In contrast, presentation of peptide/MHC complexes was inhibited with the addition of a single C-terminal flanking residue. The most dramatic inhibition was observed with isoleucine, leucine, cysteine, and proline as the C-terminal flanking residues. These residue-specific variations in presentation activity could not be accounted for by differences in the stimulatory activity of corresponding synthetic peptides but were proportional to the relative amounts of naturally processed peptides recovered in the cell extracts. These findings suggest differences in the susceptibility of N- vs C-terminal flanking residues to proteolytic cleavage during Ag processing. The strong influence of specific C-terminal flanking residue(s) could be an important factor affecting the choice of peptides presented to T cells on the APC surface.

Original languageEnglish (US)
Pages (from-to)4339-4346
Number of pages8
JournalJournal of Immunology
Volume155
Issue number9
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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