Systems and methods for immunomodulation of mucosal-associated invariant T cells
Inventors
Prlic, Martin • Berkson, Julia • Slichter, Chloe
Assignees
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Publication Number
US-12152252-B2
Publication Date
2024-11-26
Expiration Date
Abstract
Systems and methods to modulate the function of mucosal-associated invariant T (MAIT) cells in the absence of a T cell receptor (TCR) signal are described. The systems and methods can be used to elucidate the function of MAIT cells to assess potential therapeutic strategies for conditions associated with inflammation.
Core Innovation
The invention relates to inducing cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression on mucosal-associated invariant T (MAIT) cells. This induction occurs in the absence of a T cell receptor (TCR) signal by exposing MAIT cells to a defined inflammatory cytokine condition together with an anti-MR1 antibody in a single culture media.
The invention addresses MAIT-cell activation being linked to TCR signaling and MAIT activation outputs. It targets modulation of MAIT-cell function by achieving absence or reduction of TCR signal while still enabling CTLA-4 expression on MAIT cells. The disclosure also describes that anti-MR1 blocks TCR/MR1-mediated effects in a context of reduced TCR signal.
The invention includes selecting MAIT cell populations using defined MAIT phenotype markers and measuring CTLA-4 and activation readouts using assays such as RNA-seq and FACS, and multiplex/ELISA/Luminex. Documented observations report that CTLA-4 induction can occur in MAIT cells under cytokine-only stimulation even when anti-MR1 blocks MR1/TCR-mediated effects, followed by reduced MAIT activation and effector or chemokine outputs.
Claims Coverage
The document includes one independent claim covering an induction-and-measurement method, with dependent claims refining the method by adding constraints on doses, duration, and MAIT phenotype.
Ctla-4 induction on mait cells without a tcr signal
Inducing expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) on mucosal-associated invariant T (MAIT) cells in the absence of a T cell receptor (TCR) signal by incubating the MAIT cells in a single culture media with interleukin (IL)-12, IL-15, IL-18, and an anti-MR1 antibody for an effective duration of time, thereby inducing CTLA-4 on the MAIT cells in the absence of the TCR signal.
Measuring ctla-4 expression after induction
Measuring the expression of the CTLA-4 on the MAIT cells after the inducing.
Across the independent claim, CTLA-4 expression is induced on MAIT cells without a TCR signal using IL-12, IL-15, IL-18, and an anti-MR1 antibody in a single culture media for an effective duration, followed by measuring CTLA-4 expression. Dependent claims further narrow the approach with specified quantitative inputs, an effective duration, and defined MAIT phenotypes.
Stated Advantages
Enables CTLA-4 expression on MAIT cells in the absence of a TCR signal.
Documented results indicate reduced MAIT activation and effector or chemokine outputs after CTLA-4 induction.
Documented Applications
Not explicitly described in patent.
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