Peptide length preferences for rat and mouse MHC class I molecules using random peptide libraries

Eur J Immunol. 1998 Apr;28(4):1272-9. doi: 10.1002/(SICI)1521-4141(199804)28:04<1272::AID-IMMU1272>3.0.CO;2-E.


MHC class I molecules bind short peptides for presentation to CD8+ T cells. The determination of the three-dimensional structure of various MHC class I complexes has revealed that both ends of the peptide binding site are composed of polar residues conserved among all human and murine MHC class I sequences, which act to lock the ends of the peptide into the groove. In the rat, however, differences in these important residues occur, suggesting the possibility that certain rat MHC class I molecules may be able to bind and present longer peptides. Here we have studied the peptide length preferences of two rat MHC class Ia molecules expressed in the TAP2-deficient mouse cell line RMA-S: RT1-A1c, which carries unusual key residues at both ends of the groove, and RT1.Aa which carries the canonical residues. Temperature-dependent peptide stabilization assays were performed using synthetic random peptide libraries of different lengths (7-15 amino acids) and successful stabilization was determined by FACS analysis. Results for two naturally expressed mouse MHC class I molecules revealed different length preferences (H2-Kb, 8-13-mer and H2-Db, 9-15-mer peptides). The rat MHC class Ia molecule, RT1-Aa, revealed a preference for 9-15-mer peptides, whereas RT1-A1c showed a more stringent preference for 9-12-mer peptides, thereby ruling out the hypothesis that unusual residues in rat MHC molecules allow binding of longer peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Mice
  • Peptide Library
  • Peptides / chemistry
  • Protein Conformation*
  • Rats


  • Histocompatibility Antigens Class I
  • Peptide Library
  • Peptides