Immunogenetics

, Volume 39, Issue 4, pp 230–242

Pool sequencing of natural HLA-DR, DQ, and DP ligands reveals detailed peptide motifs, constraints of processing, and general rules

  • Kirsten Falk
  • Olaf Rötzschke
  • Stefan Stevanovíc
  • Günther Jung
  • Hans-Georg Rammensee
Original Articles

DOI: 10.1007/BF00188785

Cite this article as:
Falk, K., Rötzschke, O., Stevanovíc, S. et al. Immunogenetics (1994) 39: 230. doi:10.1007/BF00188785

Abstract

We have approached the problem of MHC class II ligand motifs by pool sequencing natural peptides eluted from HLA-DR, DQ, and DP molecules. The results indicate surprisingly clear patterns, although not quite as clear as with natural class I ligands. The most striking feature is a highly dominant Proline at position 2. We interpret this to be a consequence of aminopeptidase N-like activity in processing. Another general aspect is the existence of three to four hydrophobic or aromatic anchors, whereby the first and the last are separated by five to eight residues. The peptide motifs for HLA-DR1, DR5, DQ7, and DPw4 are allele-specific and differ by spacing and occupancy of anchors. The anchors tend to be flanked by clusters of charged residues, and small residues, especially Ala, are frequent in the motif centers. These detailed motifs allow one to interpret most previous (DR-) motifs as fitting one or more of the anchors or conserved clusters. The relative motif symmetry suggests the possibility of bidirectional binding of peptides in the class II groove.

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Kirsten Falk
    • 1
  • Olaf Rötzschke
    • 1
  • Stefan Stevanovíc
    • 2
  • Günther Jung
    • 2
  • Hans-Georg Rammensee
    • 1
  1. 1.Abteilung ImmungenetikMax-Planck-Institut für BiologieTübingenGermany
  2. 2.Institut für Organische ChemieUniversität TübingenTübingenGermany
  3. 3.Department of Biochemistry and Molecular BiologyHarvard UniversityCambridgeUSA
  4. 4.Tumor-virus-ImmunologieDeutsches KrebsforschungszentrumHeidelbergGermany

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