Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in <i>MR1</i>.

ABSTRACT: The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1^R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1^R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1^R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patien

SUBMITTER: Howson LJ 

PROVIDER: S-EPMC8581949 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature