Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Oct 1;176(4):1007–1013. doi: 10.1084/jem.176.4.1007

Identification of a motif for HLA-DR1 binding peptides using M13 display libraries

PMCID: PMC2119397  PMID: 1402647

Abstract

Oligonucleotides encoding peptides known to bind to HLA-DR1 molecules have been inserted into the gene III of filamentous M13 phages. DR1 molecules purified from human lymphoblastoid cell lines could specifically bind to these peptide sequences expressed on the phage surface. A M13 phage peptide library was next constructed and screened with DR1 molecules. After four rounds of selection, more than 80% of the phages were able to bind to DR1. Competition experiments with both isolated phages and corresponding synthetic peptides showed that the binding was specific. Sequence analysis of the peptide encoding region of 60 phages binding to DR1 molecules and comparison with phages of the original library revealed two potential anchor positions. The first was an aromatic residue (Tyr, Phe, or Trp) at the NH2 terminus of the peptide sequences, and the second was located three residues downstream and consisted of Met or Leu. In addition, the negatively charged amino acids Asp and Glu were mostly excluded from the DR1 binding sequences, and the small amino acid residues Gly and Ala were enriched at position 6. As for DR1, this approach should enable one to easily determine the binding motifs of other MHC class II alleles and isotypes. Furthermore, it could have interesting applications in the design of major histocompatibility complex-specific antagonists.

Full Text

The Full Text of this article is available as a PDF (682.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  2. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  3. Cwirla S. E., Peters E. A., Barrett R. W., Dower W. J. Peptides on phage: a vast library of peptides for identifying ligands. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6378–6382. doi: 10.1073/pnas.87.16.6378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Devlin J. J., Panganiban L. C., Devlin P. E. Random peptide libraries: a source of specific protein binding molecules. Science. 1990 Jul 27;249(4967):404–406. doi: 10.1126/science.2143033. [DOI] [PubMed] [Google Scholar]
  5. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  6. Glimcher L. H., Schroer J. A., Chan C., Shevach E. M. Fine specificity of cloned insulin-specific T cell hybridomas: evidence supporting a role for tertiary conformation. J Immunol. 1983 Dec;131(6):2868–2874. [PubMed] [Google Scholar]
  7. Gorga J. C., Horejsí V., Johnson D. R., Raghupathy R., Strominger J. L. Purification and characterization of class II histocompatibility antigens from a homozygous human B cell line. J Biol Chem. 1987 Nov 25;262(33):16087–16094. [PubMed] [Google Scholar]
  8. Hunt D. F., Henderson R. A., Shabanowitz J., Sakaguchi K., Michel H., Sevilir N., Cox A. L., Appella E., Engelhard V. H. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science. 1992 Mar 6;255(5049):1261–1263. doi: 10.1126/science.1546328. [DOI] [PubMed] [Google Scholar]
  9. Jardetzky T. S., Gorga J. C., Busch R., Rothbard J., Strominger J. L., Wiley D. C. Peptide binding to HLA-DR1: a peptide with most residues substituted to alanine retains MHC binding. EMBO J. 1990 Jun;9(6):1797–1803. doi: 10.1002/j.1460-2075.1990.tb08304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  11. O'Sullivan D., Arrhenius T., Sidney J., Del Guercio M. F., Albertson M., Wall M., Oseroff C., Southwood S., Colón S. M., Gaeta F. C. On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs. J Immunol. 1991 Oct 15;147(8):2663–2669. [PubMed] [Google Scholar]
  12. Panina-Bordignon P., Tan A., Termijtelen A., Demotz S., Corradin G., Lanzavecchia A. Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cells. Eur J Immunol. 1989 Dec;19(12):2237–2242. doi: 10.1002/eji.1830191209. [DOI] [PubMed] [Google Scholar]
  13. Parmley S. F., Smith G. P. Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene. 1988 Dec 20;73(2):305–318. doi: 10.1016/0378-1119(88)90495-7. [DOI] [PubMed] [Google Scholar]
  14. Rothbard J. B., Busch R., Howland K., Bal V., Fenton C., Taylor W. R., Lamb J. R. Structural analysis of a peptide--HLA class II complex: identification of critical interactions for its formation and recognition by T cell receptor. Int Immunol. 1989;1(5):479–486. doi: 10.1093/intimm/1.5.479. [DOI] [PubMed] [Google Scholar]
  15. Rothbard J. B., Gefter M. L. Interactions between immunogenic peptides and MHC proteins. Annu Rev Immunol. 1991;9:527–565. doi: 10.1146/annurev.iy.09.040191.002523. [DOI] [PubMed] [Google Scholar]
  16. Rothbard J. B., Lechler R. I., Howland K., Bal V., Eckels D. D., Sekaly R., Long E. O., Taylor W. R., Lamb J. R. Structural model of HLA-DR1 restricted T cell antigen recognition. Cell. 1988 Feb 26;52(4):515–523. doi: 10.1016/0092-8674(88)90464-3. [DOI] [PubMed] [Google Scholar]
  17. Rudensky AYu, Preston-Hurlburt P., Hong S. C., Barlow A., Janeway C. A., Jr Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991 Oct 17;353(6345):622–627. doi: 10.1038/353622a0. [DOI] [PubMed] [Google Scholar]
  18. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  19. Scott J. K., Smith G. P. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. doi: 10.1126/science.1696028. [DOI] [PubMed] [Google Scholar]
  20. Sette A., Buus S., Colon S., Smith J. A., Miles C., Grey H. M. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. 1987 Jul 30-Aug 5Nature. 328(6129):395–399. doi: 10.1038/328395a0. [DOI] [PubMed] [Google Scholar]
  21. Sinigaglia F., Romagnoli P., Guttinger M., Takacs B., Pink J. R. Selection of T cell epitopes and vaccine engineering. Methods Enzymol. 1991;203:370–386. doi: 10.1016/0076-6879(91)03021-8. [DOI] [PubMed] [Google Scholar]
  22. Todd J. A., Acha-Orbea H., Bell J. I., Chao N., Fronek Z., Jacob C. O., McDermott M., Sinha A. A., Timmerman L., Steinman L. A molecular basis for MHC class II--associated autoimmunity. Science. 1988 May 20;240(4855):1003–1009. doi: 10.1126/science.3368786. [DOI] [PubMed] [Google Scholar]
  23. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES