1klu Citations

Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.

J. Mol. Biol. 319 449-61 (2002)
Cited: 28 times
EuropePMC logo PMID: 12051920


While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies.

Articles - 1klu mentioned but not cited (11)

  1. 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)
  2. A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition. Zavala-Ruiz Z, Strug I, Walker BD, Norris PJ, Stern LJ. Proc. Natl. Acad. Sci. U.S.A. 101 13279-13284 (2004)
  3. Electrostatic modifications of the human leukocyte antigen-DR P9 peptide-binding pocket and susceptibility to primary sclerosing cholangitis. Hov JR, Kosmoliaptsis V, Traherne JA, Olsson M, Boberg KM, Bergquist A, Schrumpf E, Bradley JA, Taylor CJ, Lie BA, Trowsdale J, Karlsen TH. Hepatology 53 1967-1976 (2011)
  4. Designing coarse grained-and atom based-potentials for protein-protein docking. Tobi D. BMC Struct. Biol. 10 40 (2010)
  5. Towards universal structure-based prediction of class II MHC epitopes for diverse allotypes. Bordner AJ. PLoS ONE 5 e14383 (2010)
  6. Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model. Bordner AJ, Mittelmann HD. BMC Bioinformatics 11 41 (2010)
  7. A flexible docking approach for prediction of T cell receptor-peptide-MHC complexes. Pierce BG, Weng Z. Protein Sci. 22 35-46 (2013)
  8. Structural deformation upon protein-protein interaction: a structural alphabet approach. Martin J, Regad L, Lecornet H, Camproux AC. BMC Struct. Biol. 8 12 (2008)
  9. Deciphering the shape and deformation of secondary structures through local conformation analysis. Baussand J, Camproux AC. BMC Struct. Biol. 11 9 (2011)
  10. 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)
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Reviews citing this publication (2)

  1. A guide to the effects of a large portion of the residues of triosephosphate isomerase on catalysis, stability, druggability, and human disease. Olivares-Illana V, Riveros-Rosas H, Cabrera N, Tuena de Gómez-Puyou M, Pérez-Montfort R, Costas M, Gómez-Puyou A. Proteins 85 1190-1211 (2017)
  2. Interplay between superantigens and immunoreceptors. Petersson K, Forsberg G, Walse B. Scand. J. Immunol. 59 345-355 (2004)

Articles citing this publication (15)

  1. Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Deng L, Langley RJ, Brown PH, Xu G, Teng L, Wang Q, Gonzales MI, Callender GG, Nishimura MI, Topalian SL, Mariuzza RA. Nat. Immunol. 8 398-408 (2007)
  2. 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)
  3. A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses. Knapp B, Omasits U, Schreiner W, Epstein MM. PLoS ONE 5 e11653 (2010)
  4. Structural insights into the editing of germ-line-encoded interactions between T-cell receptor and MHC class II by Vα CDR3. Deng L, Langley RJ, Wang Q, Topalian SL, Mariuzza RA. Proc. Natl. Acad. Sci. U.S.A. 109 14960-14965 (2012)
  5. A polymorphic pocket at the P10 position contributes to peptide binding specificity in class II MHC proteins. Zavala-Ruiz Z, Strug I, Anderson MW, Gorski J, Stern LJ. Chem. Biol. 11 1395-1402 (2004)
  6. Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex. Zhao Y, Li Z, Drozd SJ, Guo Y, Mourad W, Li H. Structure 12 277-288 (2004)
  7. Structural basis for the presentation of tumor-associated MHC class II-restricted phosphopeptides to CD4+ T cells. Li Y, Depontieu FR, Sidney J, Salay TM, Engelhard VH, Hunt DF, Sette A, Topalian SL, Mariuzza RA. J. Mol. Biol. 399 596-603 (2010)
  8. Arbitrary protein-protein docking targets biologically relevant interfaces. Martin J, Lavery R. BMC Biophys 5 7 (2012)
  9. Sulfamethoxazole induces a switch mechanism in T cell receptors containing TCRVβ20-1, altering pHLA recognition. Watkins S, Pichler WJ. PLoS ONE 8 e76211 (2013)
  10. Protein expression of lymphocytes in HLA-DR transgenic pigs by a proteomic approach. Huang SY, Chen YH, Teng SH, Chen IC, Ho LL, Tu CF. Proteomics 6 5815-5825 (2006)
  11. A study of noncovalent protein complexes by matrix-assisted laser desorption/ionization. Song F. J. Am. Soc. Mass Spectrom. 18 1286-1290 (2007)
  12. Expression and bioactivity analysis of Staphylococcal enterotoxin M and N. Pan YQ, Ding D, Li DX, Chen SQ. Protein Expr. Purif. 56 286-292 (2007)
  13. CyClus: a fast, comprehensive cylindrical interface approximation clustering/reranking method for rigid-body protein-protein docking decoys. Omori S, Kitao A. Proteins 81 1005-1016 (2013)
  14. Modification of the inhibitory amino acid for epitope peptide binding onto major histocompatibility complex class II molecules enhances immunogenicity of the antigen. Chang SH, Kim J, Lee KY, Kim HJ, Chung YJ, Park CU, Kim BS, Jang YS. Scand. J. Immunol. 59 123-132 (2004)
  15. Staphylococcus enterotoxin profile of China isolates and the superantigenicity of some novel enterotoxins. Shen M, Li Y, Zhang L, Dai S, Wang J, Li Y, Zhang L, Huang J. Arch. Microbiol. 199 723-736 (2017)

Related citations provided by authors (1)

  1. Biochemical identification of a mutated human melanoma antigen recognized by CD4+ T cells. Pieper R, Christian RE, Gonzales MI, Nishimura MI, Gupta G, Settlage RE, Shabanowitz J, Rosenberg SA, Hunt DF, Topalian SL J. Exp. Med. 189 757-765 (1999)