6mff › Citations

Discriminative T-cell receptor recognition of highly homologous HLA-DQ2-bound gluten epitopes.

Dahal-Koirala S, Ciacchi L, Petersen J, Risnes LF, Neumann RS, Christophersen A, Lundin KEA, Reid HH, Qiao SW, Rossjohn J, Sollid LM
J Biol Chem 294 941-952 (2019)
Cited: 24 times
EuropePMC logo PMID: 30455354

Abstract

Celiac disease (CeD) provides an opportunity to study the specificity underlying human T-cell responses to an array of similar epitopes presented by the same human leukocyte antigen II (HLA-II) molecule. Here, we investigated T-cell responses to the two immunodominant and highly homologous HLA-DQ2.5-restricted gluten epitopes, DQ2.5-glia-α1a (PFPQPELPY) and DQ2.5-glia-ω1 (PFPQPEQPF). Using HLA-DQ2.5-DQ2.5-glia-α1a and HLA-DQ2.5-DQ2.5-glia-ω1 tetramers and single-cell αβ T-cell receptor (TCR) sequencing, we observed that despite similarity in biased variable-gene usage in the TCR repertoire responding to these nearly identical peptide-HLA-II complexes, most of the T cells are specific for either of the two epitopes. To understand the molecular basis of this exquisite fine specificity, we undertook Ala substitution assays revealing that the p7 residue (Leu/Gln) is critical for specific epitope recognition by both DQ2.5-glia-α1a- and DQ2.5-glia-ω1-reactive T-cell clones. We determined high-resolution binary crystal structures of HLA-DQ2.5 bound to DQ2.5-glia-α1a (2.0 Å) and DQ2.5-glia-ω1 (2.6 Å). These structures disclosed that differences around the p7 residue subtly alter the neighboring substructure and electrostatic properties of the HLA-DQ2.5-peptide complex, providing the fine specificity underlying the responses against these two highly homologous gluten epitopes. This study underscores the ability of TCRs to recognize subtle differences in the peptide-HLA-II landscape in a human disease setting.

Articles - 6mff mentioned but not cited (4)

  1. Discriminative T-cell receptor recognition of highly homologous HLA-DQ2-bound gluten epitopes. Dahal-Koirala S, Ciacchi L, Petersen J, Risnes LF, Neumann RS, Christophersen A, Lundin KEA, Reid HH, Qiao SW, Rossjohn J, Sollid LM. J Biol Chem 294 941-952 (2019)
  2. Structural Perspective of Gliadin Peptides Active in Celiac Disease. Falcigno L, Calvanese L, Conte M, Nanayakkara M, Barone MV, D'Auria G. Int J Mol Sci 21 E9301 (2020)
  3. HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery. Stražar M, Park J, Abelin JG, Taylor HB, Pedersen TK, Plichta DR, Brown EM, Eraslan B, Hung YM, Ortiz K, Clauser KR, Carr SA, Xavier RJ, Graham DB. Immunity 56 1681-1698.e13 (2023)
  4. Structural basis of T cell receptor specificity and cross-reactivity of two HLA-DQ2.5-restricted gluten epitopes in celiac disease. Ciacchi L, Farenc C, Dahal-Koirala S, Petersen J, Sollid LM, Reid HH, Rossjohn J. J Biol Chem 298 101619 (2022)


Reviews citing this publication (5)

  1. CRISPR/Cas9 Gene Editing of Gluten in Wheat to Reduce Gluten Content and Exposure-Reviewing Methods to Screen for Coeliac Safety. Jouanin A, Gilissen LJWJ, Schaart JG, Leigh FJ, Cockram J, Wallington EJ, Boyd LA, van den Broeck HC, van der Meer IM, America AHP, Visser RGF, Smulders MJM. Front Nutr 7 51 (2020)
  2. Recent advances in celiac disease and refractory celiac disease. Malamut G, Cording S, Cerf-Bensussan N. F1000Res 8 F1000 Faculty Rev-969 (2019)
  3. Single-cell approaches to dissect adaptive immune responses involved in autoimmunity: the case of celiac disease. Lindeman I, Sollid LM. Mucosal Immunol 15 51-63 (2022)
  4. The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer. Gouttefangeas C, Klein R, Maia A. Front Immunol 14 1212546 (2023)
  5. An Interpretable Classification Model Using Gluten-Specific TCR Sequences Shows Diagnostic Potential in Coeliac Disease. Fowler A, FitzPatrick M, Shanmugarasa A, Ibrahim ASF, Kockelbergh H, Yang HC, Williams-Walker A, Luu Hoang KN, Evans S, Provine N, Klenerman P, Soilleux EJ. Biomolecules 13 1707 (2023)

Articles citing this publication (15)

  1. T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease. Petersen J, Ciacchi L, Tran MT, Loh KL, Kooy-Winkelaar Y, Croft NP, Hardy MY, Chen Z, McCluskey J, Anderson RP, Purcell AW, Tye-Din JA, Koning F, Reid HH, Rossjohn J. Nat Struct Mol Biol 27 49-61 (2020)
  2. A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease. Ting YT, Dahal-Koirala S, Kim HSK, Qiao SW, Neumann RS, Lundin KEA, Petersen J, Reid HH, Sollid LM, Rossjohn J. Proc Natl Acad Sci U S A 117 3063-3073 (2020)
  3. Comprehensive Analysis of CDR3 Sequences in Gluten-Specific T-Cell Receptors Reveals a Dominant R-Motif and Several New Minor Motifs. Dahal-Koirala S, Risnes LF, Neumann RS, Christophersen A, Lundin KEA, Sandve GK, Qiao SW, Sollid LM. Front Immunol 12 639672 (2021)
  4. An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease. Palanski BA, Weng N, Zhang L, Hilmer AJ, Fall LA, Swaminathan K, Jabri B, Sousa C, Fernandez-Becker NQ, Khosla C, Elias JE. Nat Commun 13 888 (2022)
  5. Motifs of Three HLA-DQ Amino Acid Residues (α44, β57, β135) Capture Full Association With the Risk of Type 1 Diabetes in DQ2 and DQ8 Children. Zhao LP, Papadopoulos GK, Kwok WW, Moustakas AK, Bondinas GP, Larsson HE, Ludvigsson J, Marcus C, Samuelsson U, Wang R, Pyo CW, Nelson WC, Geraghty DE, Lernmark Å. Diabetes 69 1573-1587 (2020)
  6. Classification of intestinal T-cell receptor repertoires using machine learning methods can identify patients with coeliac disease regardless of dietary gluten status. Foers AD, Shoukat MS, Welsh OE, Donovan K, Petry R, Evans SC, FitzPatrick ME, Collins N, Klenerman P, Fowler A, Soilleux EJ. J Pathol 253 279-291 (2021)
  7. Phenotype-Based Isolation of Antigen-Specific CD4+ T Cells in Autoimmunity: A Study of Celiac Disease. Christophersen A, Dahal-Koirala S, Chlubnová M, Jahnsen J, Lundin KEA, Sollid LM. Adv Sci (Weinh) 9 e2104766 (2022)
  8. Exploring the alpha-gliadin locus: the 33-mer peptide with six overlapping coeliac disease epitopes in Triticum aestivum is derived from a subgroup of Aegilops tauschii. Schaart JG, Salentijn EMJ, Goryunova SV, Chidzanga C, Esselink DG, Gosman N, Bentley AR, Gilissen LJWJ, Smulders MJM. Plant J 106 86-94 (2021)
  9. Comparison of HLA ligand elution data and binding predictions reveals varying prediction performance for the multiple motifs recognized by HLA-DQ2.5. Koşaloğlu-Yalçın Z, Sidney J, Chronister W, Peters B, Sette A. Immunology 162 235-247 (2021)
  10. HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease. Yogeshwar SM, Muñiz-Castrillo S, Sabater L, Peris-Sempere V, Mallajosyula V, Luo G, Yan H, Yu E, Zhang J, Lin L, Fagundes Bueno F, Ji X, Picard G, Rogemond V, Pinto AL, Heidbreder A, Höftberger R, Graus F, Dalmau J, Santamaria J, Iranzo A, Schreiner B, Giannoccaro MP, Liguori R, Shimohata T, Kimura A, Ono Y, Binks S, Mariotto S, Dinoto A, Bonello M, Hartmann CJ, Tambasco N, Nigro P, Prüss H, McKeon A, Davis MM, Irani SR, Honnorat J, Gaig C, Finke C, Mignot E. Brain 147 2579-2592 (2024)
  11. Specific Genetic Polymorphisms Contributing in Differential Binding of Gliadin Peptides to HLA-DQ and TCR to Elicit Immunogenicity in Celiac Disease. Banerjee P, Chaudhary R, Singh AK, Parulekar P, Kumar S, Senapati S, Senapati S. Biochem Genet 61 2457-2480 (2023)
  12. Affinity maturation of TCR-like antibodies using phage display guided by structural modeling. Frick R, Høydahl LS, Hodnebrug I, Vik ES, Dalhus B, Sollid LM, Gray JJ, Sandlie I, Løset GÅ. Protein Eng Des Sel 35 gzac005 (2022)
  13. Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach. Atanasova M, Dimitrov I, Fernandez A, Moreno J, Koning F, Doytchinova I. Molecules 29 138 (2023)
  14. Characterisation of T cell receptor repertoires in coeliac disease. Lee LW, Shafiani S, Crossley B, Emerson RO, Williamson D, Bunin A, Vargas J, Han AS, Kaplan IM, Green PHR, Kirsch I, Bhagat G. J Clin Pathol 77 116-124 (2024)
  15. Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease. Okura Y, Ikawa-Teranishi Y, Mizoroki A, Takahashi N, Tsushima T, Irie M, Harfuddin Z, Miura-Okuda M, Ito S, Nakamura G, Takesue H, Ozono Y, Nishihara M, Yamada K, Gan SW, Hayasaka A, Ishii S, Wakabayashi T, Muraoka M, Nagaya N, Hino H, Nemoto T, Kuramochi T, Torizawa T, Shimada H, Kitazawa T, Okazaki M, Nezu J, Sollid LM, Igawa T. Nat Commun 14 8502 (2023)


Quick links