3pdo Citations

Bidirectional binding of invariant chain peptides to an MHC class II molecule.

Proc. Natl. Acad. Sci. U.S.A. 107 22219-24 (2010)
Related entries: 3pgc, 3pgd

Cited: 27 times
EuropePMC logo PMID: 21115828


T-cell recognition of peptides bound to MHC class II (MHCII) molecules is a central event in cell-mediated adaptive immunity. The current paradigm holds that prebound class II-associated invariant chain peptides (CLIP) and all subsequent antigens maintain a canonical orientation in the MHCII binding groove. Here we provide evidence for MHCII-bound CLIP inversion. NMR spectroscopy demonstrates that the interconversion from the canonical to the inverse alignment is a dynamic process, and X-ray crystallography shows that conserved MHC residues form a hydrogen bond network with the peptide backbone in both orientations. The natural catalyst HLA-DM accelerates peptide reorientation and the exchange of either canonically or inversely bound CLIP against antigenic peptide. Thus, noncanonical MHC-CLIP displays the hallmarks of a structurally and functionally intact antigen-presenting complex.

Articles - 3pdo mentioned but not cited (5)

  1. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA, Raj T, IMSGC, ANZgene, Gourraud PA, Stranger BE, Oksenberg J, Olsson T, Taylor BV, Sawcer S, Hafler DA, Carrington M, De Jager PL, de Bakker PI. PLoS Genet. 9 e1003926 (2013)
  2. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Goyette P, Boucher G, Mallon D, Ellinghaus E, Jostins L, Huang H, Ripke S, Gusareva ES, Annese V, Hauser SL, Oksenberg JR, Thomsen I, Leslie S, International Inflammatory Bowel Disease Genetics Consortium, Australia and New Zealand IBDGC, Belgium IBD Genetics Consortium, Italian Group for IBD Genetic Consortium, NIDDK Inflammatory Bowel Disease Genetics Consortium, United Kingdom IBDGC, Wellcome Trust Case Control Consortium, Quebec IBD Genetics Consortium, Daly MJ, Van Steen K, Duerr RH, Barrett JC, McGovern DP, Schumm LP, Traherne JA, Carrington MN, Kosmoliaptsis V, Karlsen TH, Franke A, Rioux JD. Nat. Genet. 47 172-179 (2015)
  3. Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates. Dijkstra JM, Grimholt U, Leong J, Koop BF, Hashimoto K. BMC Evol. Biol. 13 260 (2013)
  4. pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity. Jiang W, Strohman MJ, Somasundaram S, Ayyangar S, Hou T, Wang N, Mellins ED. Sci Rep 5 17333 (2015)
  5. An effective and effecient peptide binding prediction approach for a broad set of HLA-DR molecules based on ordered weighted averaging of binding pocket profiles. Shen WJ, Zhang S, Wong HS. Proteome Sci 11 S15 (2013)

Reviews citing this publication (3)

  1. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation. Wieczorek M, Abualrous ET, Sticht J, Álvaro-Benito M, Stolzenberg S, Noé F, Freund C. Front Immunol 8 292 (2017)
  2. The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway. Schulze MS, Wucherpfennig KW. Curr. Opin. Immunol. 24 105-111 (2012)
  3. Conformational variation in structures of classical and non-classical MHCII proteins and functional implications. Painter CA, Stern LJ. Immunol. Rev. 250 144-157 (2012)

Articles citing this publication (19)

  1. Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations. Okada Y, Kim K, Han B, Pillai NE, Ong RT, Saw WY, Luo M, Jiang L, Yin J, Bang SY, Lee HS, Brown MA, Bae SC, Xu H, Teo YY, de Bakker PI, Raychaudhuri S. Hum. Mol. Genet. 23 6916-6926 (2014)
  2. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Fernandez CA, Smith C, Yang W, Daté M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. Blood 124 1266-1276 (2014)
  3. Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. Schlundt A, Heinz GA, Janowski R, Geerlof A, Stehle R, Heissmeyer V, Niessing D, Sattler M. Nat. Struct. Mol. Biol. 21 671-678 (2014)
  4. 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)
  5. HLA-DRα1 constructs block CD74 expression and MIF effects in experimental autoimmune encephalomyelitis. Meza-Romero R, Benedek G, Yu X, Mooney JL, Dahan R, Duvshani N, Bucala R, Offner H, Reiter Y, Burrows GG, Vandenbark AA. J. Immunol. 192 4164-4173 (2014)
  6. 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)
  7. Susceptibility to HLA-DM protein is determined by a dynamic conformation of major histocompatibility complex class II molecule bound with peptide. Yin L, Trenh P, Guce A, Wieczorek M, Lange S, Sticht J, Jiang W, Bylsma M, Mellins ED, Freund C, Stern LJ. J. Biol. Chem. 289 23449-23464 (2014)
  8. Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility to multiple sclerosis in Sardinia: a molecular dynamics simulation study. Kumar A, Cocco E, Atzori L, Marrosu MG, Pieroni E. PLoS ONE 8 e59711 (2013)
  9. NMR spectroscopy reveals unexpected structural variation at the protein-protein interface in MHC class I molecules. Beerbaum M, Ballaschk M, Erdmann N, Schnick C, Diehl A, Uchanska-Ziegler B, Ziegler A, Schmieder P. J. Biomol. NMR 57 167-178 (2013)
  10. Gauche(+) side-chain orientation as a key factor in the search for an immunogenic peptide mixture leading to a complete fully protective vaccine. Bermúdez A, Calderon D, Moreno-Vranich A, Almonacid H, Patarroyo MA, Poloche A, Patarroyo ME. Vaccine 32 2117-2126 (2014)
  11. Peptide linkage to the α-subunit of MHCII creates a stably inverted antigen presentation complex. Schlundt A, Günther S, Sticht J, Wieczorek M, Roske Y, Heinemann U, Freund C. J. Mol. Biol. 423 294-302 (2012)
  12. MHC class II complexes sample intermediate states along the peptide exchange pathway. Wieczorek M, Sticht J, Stolzenberg S, Günther S, Wehmeyer C, El Habre Z, Álvaro-Benito M, Noé F, Freund C. Nat Commun 7 13224 (2016)
  13. Novel in silico tools for designing peptide-based subunit vaccines and immunotherapeutics. Dhanda SK, Usmani SS, Agrawal P, Nagpal G, Gautam A, Raghava GPS. Brief. Bioinformatics 18 467-478 (2017)
  14. HLA-DP2 binding prediction by molecular dynamics simulations. Doytchinova I, Petkov P, Dimitrov I, Atanasova M, Flower DR. Protein Sci. 20 1918-1928 (2011)
  15. Anti-LGI1 encephalitis is associated with unique HLA subtypes. Kim TJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, Shin YW, Jun JS, Lee HS, Lee WJ, Yang AR, Choi Y, Park KI, Jung KH, Jung KY, Kim M, Lee SK, Chu K. Ann. Neurol. 81 183-192 (2017)
  16. Antigenic peptide molecular recognition by the DRB1-DQB1 haplotype modulates multiple sclerosis susceptibility. Kumar A, Melis P, Genna V, Cocco E, Marrosu MG, Pieroni E. Mol Biosyst 10 2043-2054 (2014)
  17. Flanking residues are central to DO11.10 T cell hybridoma stimulation by ovalbumin 323-339. Roy BM, Zhukov DV, Maynard JA. PLoS ONE 7 e47585 (2012)
  18. HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption. Moon J, Kim TJ, Lim JA, Sunwoo JS, Byun JI, Lee ST, Jung KH, Park KI, Jung KY, Jeon D, Yu KS, Jang IJ, Chu K, Lee SK. Epilepsia 57 1879-1886 (2016)
  19. HLA-DR7 and HLA-DQ2: Transgenic mouse strains tested as a model system for ximelagatran hepatotoxicity. Lundgren H, Martinsson K, Cederbrant K, Jirholt J, Mucs D, Madeyski-Bengtson K, Havarinasab S, Hultman P. PLoS ONE 12 e0184744 (2017)