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Conformational restraints and flexibility of 14-meric peptides in complex with HLA-B*3501.

Probst-Kepper M, Hecht HJ, Herrmann H, Janke V, Ocklenburg F, Klempnauer J, van den Eynde BJ, Weiss S
J Immunol 173 5610-6 (2004)
Cited: 56 times
EuropePMC logo PMID: 15494511

Abstract

Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from an alternative reading frame of M-CSF with high affinity. Due to its extraordinary length, the exact HLA binding mode was unpredictable. The crystal structure of HLA-B*3501 at 1.5 A shows that the N and C termini of the peptide are embedded in the A and F pockets, respectively, similar to a peptide of normal length. The central part of the 14-meric peptide bulges flexibly out of the groove. Two variants of the alternative reading frame of M-CSF peptide substituted at P2 or P2 and P9 with Ala display weak or no T cell activation. Their structure differs mainly in flexibility and conformation from the agonistic peptide. Moreover, the variants induce subtle changes of MHC alpha-helical regions implicated as critical for TCR contact. The TCR specifically recognizing this peptide/MHC complex exhibits CDR3 length within the normal range, suggesting major conformational adaptations of this receptor upon peptide/MHC binding. Thus, the potential antigenic repertoire recognizable by CTLs is larger than currently thought.

Reviews - 1xh3 mentioned but not cited (1)

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Articles - 1xh3 mentioned but not cited (11)

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Reviews citing this publication (11)

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Articles citing this publication (33)

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  4. Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding. Koch M, Camp S, Collen T, Avila D, Salomonsen J, Wallny HJ, van Hateren A, Hunt L, Jacob JP, Johnston F, Marston DA, Shaw I, Dunbar PR, Cerundolo V, Jones EY, Kaufman J. Immunity 27 885-899 (2007)
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  6. Structures of MART-126/27-35 Peptide/HLA-A2 complexes reveal a remarkable disconnect between antigen structural homology and T cell recognition. Borbulevych OY, Insaidoo FK, Baxter TK, Powell DJ, Johnson LA, Restifo NP, Baker BM. J Mol Biol 372 1123-1136 (2007)
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  10. Enhanced detection of human immunodeficiency virus type 1 (HIV-1) Nef-specific T cells recognizing multiple variants in early HIV-1 infection. Malhotra U, Li F, Nolin J, Allison M, Zhao H, Mullins JI, Self S, McElrath MJ. J Virol 81 5225-5237 (2007)
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  12. MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors. Macdonald IK, Harkiolaki M, Hunt L, Connelley T, Carroll AV, MacHugh ND, Graham SP, Jones EY, Morrison WI, Flower DR, Ellis SA. PLoS Pathog 6 e1001149 (2010)
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  14. The peptide length specificity of some HLA class I alleles is very broad and includes peptides of up to 25 amino acids in length. Bell MJ, Burrows JM, Brennan R, Miles JJ, Tellam J, McCluskey J, Rossjohn J, Khanna R, Burrows SR. Mol Immunol 46 1911-1917 (2009)
  15. Highly divergent T-cell receptor binding modes underlie specific recognition of a bulged viral peptide bound to a human leukocyte antigen class I molecule. Liu YC, Miles JJ, Neller MA, Gostick E, Price DA, Purcell AW, McCluskey J, Burrows SR, Rossjohn J, Gras S. J Biol Chem 288 15442-15454 (2013)
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  17. Increased diversity of the HLA-B40 ligandome by the presentation of peptides phosphorylated at their main anchor residue. Marcilla M, Alpízar A, Lombardía M, Ramos-Fernandez A, Ramos M, Albar JP. Mol Cell Proteomics 13 462-474 (2014)
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  26. Cytotoxic T cell immunity against the non-immunogenic, murine, hepatocellular carcinoma Hepa1-6 is directed towards the novel alternative form of macrophage colony stimulating factor. Ge L, Zhang JG, Samathanam CA, Delgado C, Tarbiyat-Boldaji M, Dan Q, Hoa N, Nguyen TV, Alipanah R, Pham JT, Sanchez R, Wepsic HT, Morgan TR, Jadus MR. Cell Immunol 259 117-127 (2009)
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  29. Combining Well-Tempered Metadynamics Simulation and SPR Assays to Characterize the Binding Mechanism of the Universal T-Lymphocyte Tetanus Toxin Epitope TT830-843. Brandt AAML, Rodrigues-da-Silva RN, Lima-Junior JC, Alves CR, de Souza-Silva F. Biomed Res Int 2021 5568980 (2021)
  30. The polymorphism at residue 156 determines the HLA-B*35 restricted peptide repertoire during HCMV infection. Abels WC, Manandhar T, Kunze-Schumacher H, Blasczyk R, Bade-Döding C. Immunogenetics 70 639-646 (2018)
  31. A Quantum Vaccinomics Approach for the Design and Production of MSP4 Chimeric Antigen for the Control of Anaplasma phagocytophilum Infections. de la Fuente J, Moraga-Fernández A, Alberdi P, Díaz-Sánchez S, García-Álvarez O, Fernández-Melgar R, Contreras M. Vaccines (Basel) 10 1995 (2022)
  32. Determination of T Cell Responses in Thai Systemic Sclerosis Patients. Likhit O, Louthrenoo W, Pattanakitsakul SN, Suttitheptumrong A, Hannongbua S, Rungrotmongkol T, Noguchi H, Takeuchi F, Boonnak K. J Immunol Res 2022 5072154 (2022)
  33. Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. Pymm P, Tenzer S, Wee E, Weimershaus M, Burgevin A, Kollnberger S, Gerstoft J, Josephs TM, Ladell K, McLaren JE, Appay V, Price DA, Fugger L, Bell JI, Schild H, van Endert P, Harkiolaki M, Iversen AKN. Cell Rep 38 110449 (2022)


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