Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity - PubMed (original) (raw)
Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity
Jennifer Maynard et al. Immunity. 2005 Jan.
Free article
Abstract
T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vbeta domain of the TCR, which interacts with the MHC alpha chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.
Similar articles
- Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
Li Y, Huang Y, Lue J, Quandt JA, Martin R, Mariuzza RA. Li Y, et al. EMBO J. 2005 Sep 7;24(17):2968-79. doi: 10.1038/sj.emboj.7600771. Epub 2005 Aug 4. EMBO J. 2005. PMID: 16079912 Free PMC article. - A molecular basis for how a single TCR interfaces multiple ligands.
Boesteanu A, Brehm M, Mylin LM, Christianson GJ, Tevethia SS, Roopenian DC, Joyce S. Boesteanu A, et al. J Immunol. 1998 Nov 1;161(9):4719-27. J Immunol. 1998. PMID: 9794402 - Structural requirements for binding of myelin basic protein (MBP) peptides to MHC II: effects on immune regulation.
Mantzourani ED, Mavromoustakos TM, Platts JA, Matsoukas JM, Tselios TV. Mantzourani ED, et al. Curr Med Chem. 2005;12(13):1521-35. doi: 10.2174/0929867054039053. Curr Med Chem. 2005. PMID: 15974985 Review. - TCR recognition of peptide/MHC class II complexes and superantigens.
Sundberg EJ, Deng L, Mariuzza RA. Sundberg EJ, et al. Semin Immunol. 2007 Aug;19(4):262-71. doi: 10.1016/j.smim.2007.04.006. Epub 2007 Jun 7. Semin Immunol. 2007. PMID: 17560120 Free PMC article. Review.
Cited by
- HLA-transgenic mouse models to study autoimmune central nervous system diseases.
Pressley KR, Schwegman L, Montes De Oca Arena M, Chase Huizar C, Zamvil SS, Forsthuber TG. Pressley KR, et al. Autoimmunity. 2024 Dec;57(1):2387414. doi: 10.1080/08916934.2024.2387414. Epub 2024 Aug 21. Autoimmunity. 2024. PMID: 39167553 Review. - 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. Gouttefangeas C, et al. Front Immunol. 2023 Jun 19;14:1212546. doi: 10.3389/fimmu.2023.1212546. eCollection 2023. Front Immunol. 2023. PMID: 37409132 Free PMC article. Review. - MHC Class II Presentation in Autoimmunity.
Ishina IA, Zakharova MY, Kurbatskaia IN, Mamedov AE, Belogurov AA Jr, Gabibov AG. Ishina IA, et al. Cells. 2023 Jan 14;12(2):314. doi: 10.3390/cells12020314. Cells. 2023. PMID: 36672249 Free PMC article. Review. - A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry.
Singh NK, Alonso JA, Devlin JR, Keller GLJ, Gray GI, Chiranjivi AK, Foote SG, Landau LM, Arbuiso AG, Weiss LI, Rosenberg AM, Hellman LM, Nishimura MI, Baker BM. Singh NK, et al. Nat Commun. 2022 Nov 23;13(1):7189. doi: 10.1038/s41467-022-34896-0. Nat Commun. 2022. PMID: 36424374 Free PMC article. - Cross-reactivity of SARS-CoV-2- and influenza A-specific T cells in individuals exposed to SARS-CoV-2.
Chaisawangwong W, Wang H, Kouo T, Salathe SF, Isser A, Bieler JG, Zhang ML, Livingston NK, Li S, Horowitz JJ, Samet RE, Zyskind I, Rosenberg AZ, Schneck JP. Chaisawangwong W, et al. JCI Insight. 2022 Sep 22;7(18):e158308. doi: 10.1172/jci.insight.158308. JCI Insight. 2022. PMID: 36134660 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
- CA-78040/CA/NCI NIH HHS/United States
- AI-48540/AI/NIAID NIH HHS/United States
- AI-22519/AI/NIAID NIH HHS/United States
- HL077325/HL/NHLBI NIH HHS/United States
- F32 AI055245/AI/NIAID NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous