1sjh Citations

A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition.

Proc. Natl. Acad. Sci. U.S.A. 101 13279-84 (2004)
Cited: 31 times
EuropePMC logo PMID: 15331779


T cells generally recognize peptide antigens bound to MHC proteins through contacts with residues found within or immediately flanking the seven- to nine-residue sequence accommodated in the MHC peptide-binding groove. However, some T cells require peptide residues outside this region for activation, the structural basis for which is unknown. Here, we have investigated a HIV Gag-specific T cell clone that requires an unusually long peptide antigen for activation. The crystal structure of a minimally antigenic 16-mer bound to HLA-DR1 shows that the peptide C-terminal region bends sharply into a hairpin turn as it exits the binding site, orienting peptide residues outside the MHC-binding region in position to interact with a T cell receptor. Peptide truncation and substitution studies show that both the hairpin turn and the extreme C-terminal residues are required for T cell activation. These results demonstrate a previously unrecognized mode of MHC-peptide-T cell receptor interaction.

Articles - 1sjh mentioned but not cited (3)

Reviews citing this publication (4)

  1. Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings. Ayres CM, Corcelli SA, Baker BM. Front Immunol 8 935 (2017)
  2. HLA-DR: molecular insights and vaccine design. Stern LJ, Calvo-Calle JM. Curr. Pharm. Des. 15 3249-3261 (2009)
  3. The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes. Sant AJ, Chaves FA, Jenks SA, Richards KA, Menges P, Weaver JM, Lazarski CA. Immunol. Rev. 207 261-278 (2005)
  4. Conformational isomers of a peptide-class II major histocompatibility complex. Lovitch SB, Unanue ER. Immunol. Rev. 207 293-313 (2005)

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  2. Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults. Su LF, Kidd BA, Han A, Kotzin JJ, Davis MM. Immunity 38 373-383 (2013)
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  4. Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores. Salomon J, Flower DR. BMC Bioinformatics 7 501 (2006)
  5. Human CD4+ T cell epitopes from vaccinia virus induced by vaccination or infection. Calvo-Calle JM, Strug I, Nastke MD, Baker SP, Stern LJ. PLoS Pathog. 3 1511-1529 (2007)
  6. DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype. Durinovic-Belló I, Rosinger S, Olson JA, Congia M, Ahmad RC, Rickert M, Hampl J, Kalbacher H, Drijfhout JW, Mellins ED, Al Dahouk S, Kamradt T, Maeurer MJ, Nhan C, Roep BO, Boehm BO, Polychronakos C, Nepom GT, Karges W, McDevitt HO, Sønderstrup G. Proc. Natl. Acad. Sci. U.S.A. 103 11683-11688 (2006)
  7. Association of BLV infection profiles with alleles of the BoLA-DRB3.2 gene. Juliarena MA, Poli M, Sala L, Ceriani C, Gutierrez S, Dolcini G, Rodríguez EM, Mariño B, Rodríguez-Dubra C, Esteban EN. Anim. Genet. 39 432-438 (2008)
  8. HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia virus by favoring the presentation of peptides with longer HLA-DM-mediated half-lives. Yin L, Calvo-Calle JM, Dominguez-Amorocho O, Stern LJ. J. Immunol. 189 3983-3994 (2012)
  9. Characterization of structural features controlling the receptiveness of empty class II MHC molecules. Rupp B, Günther S, Makhmoor T, Schlundt A, Dickhaut K, Gupta S, Choudhary I, Wiesmüller KH, Jung G, Freund C, Falk K, Rötzschke O, Kühne R. PLoS ONE 6 e18662 (2011)
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  11. Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background. Knapp B, Fischer G, Van Hemelen D, Fae I, Maillere B, Ebner C, Schreiner W, Bohle B, Jahn-Schmid B. BMC Immunol. 13 43 (2012)
  12. Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58. Gokhale A, Weldeghiorghis TK, Taneja V, Satyanarayanajois SD. J. Med. Chem. 54 5307-5319 (2011)
  13. Re-Directing CD4(+) T Cell Responses with the Flanking Residues of MHC Class II-Bound Peptides: The Core is Not Enough. Holland CJ, Cole DK, Godkin A. Front Immunol 4 172 (2013)
  14. Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope. Norris PJ, Stone JD, Anikeeva N, Heitman JW, Wilson IC, Hirschkorn DF, Clark MJ, Moffett HF, Cameron TO, Sykulev Y, Stern LJ, Walker BD. Mol. Immunol. 43 1349-1357 (2006)
  15. Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4⁺ T-cell repertoire selection. Cole DK, Gallagher K, Lemercier B, Holland CJ, Junaid S, Hindley JP, Wynn KK, Gostick E, Sewell AK, Gallimore AM, Ladell K, Price DA, Gougeon ML, Godkin A. Nat Commun 3 665 (2012)
  16. Folding of an MHC class II-restricted tumor antigen controls its antigenicity via MHC-guided processing. Mimura Y, Mimura-Kimura Y, Doores K, Golgher D, Davis BG, Dwek RA, Rudd PM, Elliott T. Proc. Natl. Acad. Sci. U.S.A. 104 5983-5988 (2007)
  17. PREDIVAC: CD4+ T-cell epitope prediction for vaccine design that covers 95% of HLA class II DR protein diversity. Oyarzún P, Ellis JJ, Bodén M, Kobe B. BMC Bioinformatics 14 52 (2013)
  18. A photocontrolled beta-hairpin peptide. Dong SL, Löweneck M, Schrader TE, Schreier WJ, Zinth W, Moroder L, Renner C. Chemistry 12 1114-1120 (2006)
  19. Synthesis and structural investigations of functionalizable hybrid β-hairpin. Bandyopadhyay A, Mali SM, Lunawat P, Raja KM, Gopi HN. Org. Lett. 13 4482-4485 (2011)
  20. Synthesis of a 6,6-spiroketal amino acid and its incorporation into a peptide turn sequence using solid-phase peptide synthesis. Kueh JT, Choi KW, Williams GM, Moehle K, Bacsa B, Robinson JA, Brimble MA. Chemistry 19 3807-3811 (2013)
  21. MHC Class II Binding Prediction by Molecular Docking. Atanasova M, Dimitrov I, Flower DR, Doytchinova I. Mol Inform 30 368-375 (2011)
  22. Elongating modified conserved peptides eliminates their immunogenicity and protective efficacy against P. falciparum malaria. Espejo F, Bermúdez A, Vanegas M, Rivera Z, Torres E, Salazar LM, Patarroyo ME. J. Struct. Biol. 150 245-258 (2005)
  23. Conformation study of HA(306-318) antigenic peptide of the haemagglutinin influenza virus protein. Bertrand A, Brito RM, Alix AJ, Lancelin JM, Carvalho RA, Geraldes CF, Lakhdar-Ghazal F. Spectrochim Acta A Mol Biomol Spectrosc 65 711-718 (2006)
  24. A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function. Jacobs ES, Persad D, Ran L, Danesh A, Heitman JW, Deng X, Cameron MJ, Kelvin DJ, Norris PJ. Retrovirology 11 57 (2014)