MAIT cell recognition of MR1 on bacterially infected and uninfected cells.
Mucosal-associated invariant T cells are a unique population of T cells that express a semi-invariant αβ TCR and are restricted by the MHC class I-related molecule MR1. MAIT cells recognize uncharacterized ligand(s) presented by MR1 through the cognate interaction between their TCR and MR1. To understand how the MAIT TCR recognizes MR1 at the surface of APCs cultured both with and without bacteria, we undertook extensive mutational analysis of both the MAIT TCR and MR1 molecule. We found differential contribution of particular amino acids to the MAIT TCR-MR1 interaction based upon the presence of bacteria, supporting the hypothesis that the structure of the MR1 molecules with the microbial-derived ligand(s) differs from the one with the endogenous ligand(s). Furthermore, we demonstrate that microbial-derived ligand(s) is resistant to proteinase K digestion and does not extract with common lipids, suggesting an unexpected class of antigen(s) might be recognized by this unique lymphocyte population.
Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, United States of America.
Mary H
MH
Young
Lance
L
U'Ren
Shouxiong
S
Huang
Thierry
T
Mallevaey
James
J
Scott-Browne
Frances
F
Crawford
Olivier
O
Lantz
Ted H
TH
Hansen
John
J
Kappler
Philippa
P
Marrack
Laurent
L
Gapin
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D019286:Endopeptidase K / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D016296:Mutagenesis; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D059748:Proteolysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*
D000942:Antigens, Bacterial; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D019286:Endopeptidase K