Evidence for MR1 antigen presentation to mucosal-associated invariant T cells

Shouxiong Huang, Susan Gilfillan, Marina Cella, Michael J. Miley, Olivier Lantz, Lonnie Lybarger, Daved H. Fremont, Ted H. Hansen

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

The novel class Ib molecule MR1 is highly conserved in mammals, particularly in its α1/α2 domains. Recent studies demonstrated that MR1 expression is required for development and expansion of a small population of T cells expressing an invariant T cell receptor (TCR) α chain called mucosal-associated invariant T (MAIT) cells. Despite these intriguing properties it has been difficult to determine whether MR1 expression and MAIT cell recognition is ligand-dependent. To address these outstanding questions, monoclonal antibodies were produced in MR1 knock-out mice immunized with recombinant MR1 protein, and a series of MR1 mutations were generated at sites previously shown to disrupt the ability of class Ia molecules to bind peptide or TCR. Here we show that 1) MR1 molecules are detected by monoclonal antibodies in either an open or folded conformation that correlates precisely with peptide-induced conformational changes in class Ia molecules, 2) only the folded MR1 conformer activated 2/2 MAIT hybridoma cells tested, 3) the pattern of MAIT cell activation by the MR1 mutants implies the MR1/TCR orientation is strikingly similar to published major histocompatibility complex/ αβTCR engagements, 4) all the MR1 mutations tested and found to severely reduce surface expression of folded molecules were located in the putative ligand binding groove, and 5) certain groove mutants of MR1 that are highly expressed on the cell surface disrupt MAIT cell activation. These combined data strongly support the conclusion that MR1 has an antigen presentation function.

Original languageEnglish (US)
Pages (from-to)21183-21193
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number22
DOIs
StatePublished - Jun 3 2005

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T-cells
Antigen Presentation
T-Cell Antigen Receptor
Antigens
Molecules
Chemical activation
Monoclonal Antibodies
Ligands
Peptide T
Recombinant proteins
Peptides
Mutation
Mammals
Hybridomas
Major Histocompatibility Complex
Recombinant Proteins
Knockout Mice
Conformations
Mucosal-Associated Invariant T Cells
T-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Huang, S., Gilfillan, S., Cella, M., Miley, M. J., Lantz, O., Lybarger, L., ... Hansen, T. H. (2005). Evidence for MR1 antigen presentation to mucosal-associated invariant T cells. Journal of Biological Chemistry, 280(22), 21183-21193. https://doi.org/10.1074/jbc.M501087200

Evidence for MR1 antigen presentation to mucosal-associated invariant T cells. / Huang, Shouxiong; Gilfillan, Susan; Cella, Marina; Miley, Michael J.; Lantz, Olivier; Lybarger, Lonnie; Fremont, Daved H.; Hansen, Ted H.

In: Journal of Biological Chemistry, Vol. 280, No. 22, 03.06.2005, p. 21183-21193.

Research output: Contribution to journalArticle

Huang, S, Gilfillan, S, Cella, M, Miley, MJ, Lantz, O, Lybarger, L, Fremont, DH & Hansen, TH 2005, 'Evidence for MR1 antigen presentation to mucosal-associated invariant T cells', Journal of Biological Chemistry, vol. 280, no. 22, pp. 21183-21193. https://doi.org/10.1074/jbc.M501087200
Huang, Shouxiong ; Gilfillan, Susan ; Cella, Marina ; Miley, Michael J. ; Lantz, Olivier ; Lybarger, Lonnie ; Fremont, Daved H. ; Hansen, Ted H. / Evidence for MR1 antigen presentation to mucosal-associated invariant T cells. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 22. pp. 21183-21193.
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