The MAIT TCRβ chain contributes to discrimination of microbial ligand
Gitanjali A Narayanan
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
Search for more papers by this authorJames E McLaren
Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Search for more papers by this authorErin W Meermeier
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
Search for more papers by this authorKristin Ladell
Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Search for more papers by this authorGwendolyn M Swarbrick
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
VA Portland Health Care Center, Portland, OR, USA
Search for more papers by this authorDavid A Price
Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Systems Immunity Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Search for more papers by this authorJessica G Tran
VA Portland Health Care Center, Portland, OR, USA
Search for more papers by this authorAneta H Worley
VA Portland Health Care Center, Portland, OR, USA
Search for more papers by this authorEmily B Wong
Africa Health Research Institute, Durban, South Africa
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
Harvard Medical School, Boston, MA, USA
Search for more papers by this authorCorresponding Author
David M Lewinsohn
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
VA Portland Health Care Center, Portland, OR, USA
Correspondence
David M Lewinsohn, Pulmonary and Critical Care Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Mail Code VA R&D 11, Portland, OR 97239, USA.
E-mail: [email protected]
Search for more papers by this authorGitanjali A Narayanan
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
Search for more papers by this authorJames E McLaren
Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Search for more papers by this authorErin W Meermeier
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
Search for more papers by this authorKristin Ladell
Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Search for more papers by this authorGwendolyn M Swarbrick
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
VA Portland Health Care Center, Portland, OR, USA
Search for more papers by this authorDavid A Price
Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Systems Immunity Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Search for more papers by this authorJessica G Tran
VA Portland Health Care Center, Portland, OR, USA
Search for more papers by this authorAneta H Worley
VA Portland Health Care Center, Portland, OR, USA
Search for more papers by this authorEmily B Wong
Africa Health Research Institute, Durban, South Africa
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
Harvard Medical School, Boston, MA, USA
Search for more papers by this authorCorresponding Author
David M Lewinsohn
Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
VA Portland Health Care Center, Portland, OR, USA
Correspondence
David M Lewinsohn, Pulmonary and Critical Care Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Mail Code VA R&D 11, Portland, OR 97239, USA.
E-mail: [email protected]
Search for more papers by this authorAbstract
Mucosal-associated invariant T (MAIT) cells are key players in the immune response against microbial infection. The MAIT T-cell receptor (TCR) recognizes a diverse array of microbial ligands, and recent reports have highlighted the variability in the MAIT TCR that could further contribute to discrimination of ligand. The MAIT TCR complementarity determining region (CDR)3β sequence displays a high level of diversity across individuals, and clonotype usage appears to be dependent on antigenic exposure. To address the relationship between the MAIT TCR and microbial ligand, we utilized a previously defined panel of MAIT cell clones that demonstrated variability in responses against different microbial infections. Sequencing of these clones revealed four pairs, each with shared (identical) CDR3α and different CDR3β sequences. These pairs demonstrated varied responses against microbially infected dendritic cells as well as against 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil, a ligand abundant in Salmonella enterica serovar Typhimurium, suggesting that the CDR3β contributes to differences in ligand discrimination. Taken together, these results highlight a key role for the MAIT CDR3β region in distinguishing between MR1-bound antigens and ligands.
Conflict of Interest
The authors declare no conflict of interest.
Supporting Information
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