αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands

Richard W Birkinshaw, Daniel G Pellicci, Tan-Yun Cheng, Andrew N Keller, Maria L Sandoval-Romero, Stephanie Gras, Annemieke de Jong, Adam P Uldrich, D Branch Moody, Dale I Godfrey, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

54 Citations (Scopus)

Abstract

A central paradigm in alphabeta T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the alphabeta T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby alphabeta T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.
Original languageEnglish
Pages (from-to)258-266
Number of pages9
JournalNature Immunology
Volume16
Issue number3
DOIs
Publication statusPublished - 2015

Cite this

Birkinshaw, Richard W ; Pellicci, Daniel G ; Cheng, Tan-Yun ; Keller, Andrew N ; Sandoval-Romero, Maria L ; Gras, Stephanie ; de Jong, Annemieke ; Uldrich, Adam P ; Moody, D Branch ; Godfrey, Dale I ; Rossjohn, Jamie. / αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands. In: Nature Immunology. 2015 ; Vol. 16, No. 3. pp. 258-266.
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abstract = "A central paradigm in alphabeta T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the alphabeta T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby alphabeta T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.",
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Birkinshaw, RW, Pellicci, DG, Cheng, T-Y, Keller, AN, Sandoval-Romero, ML, Gras, S, de Jong, A, Uldrich, AP, Moody, DB, Godfrey, DI & Rossjohn, J 2015, 'αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands', Nature Immunology, vol. 16, no. 3, pp. 258-266. https://doi.org/10.1038/ni.3098

αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands. / Birkinshaw, Richard W; Pellicci, Daniel G; Cheng, Tan-Yun; Keller, Andrew N; Sandoval-Romero, Maria L; Gras, Stephanie; de Jong, Annemieke; Uldrich, Adam P; Moody, D Branch; Godfrey, Dale I; Rossjohn, Jamie.

In: Nature Immunology, Vol. 16, No. 3, 2015, p. 258-266.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gras, Stephanie

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AU - Uldrich, Adam P

AU - Moody, D Branch

AU - Godfrey, Dale I

AU - Rossjohn, Jamie

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