This is an interesting manuscript providing characterization of TCR or cytokine-stimulated liver-derived MAIT cells and showing differences between ld MAITs and blood MAITs. Authors show that ld MAIT cells are different to blood MAIT cells in their responsiveness to cytokine stimulation. Transcriptomic analysis of blood and ld MAIT cells also showed fundamental differences in fatty-acid metabolism and oxidative phosphorylation. This manuscript is well written and experiments are well-designed, conclusions were well-supported by the experimental results. I recommend that this paper can be accepted after minor revisions. Some suggestions are detailed below:
Major comments:
- Line 72- It is known that aging is associated with reduced circulating MAIT cells and altered cytokine profiles. Ages of the human subjects and total number of patients recruited from which samples were taken should be mentioned.

• Line 162 - Activation induced transcriptomic profile is compared between liver and blood MAITs (S. figure 5). Why different concentration of 5-A-RU was used for blood (5 µM) vs. for liver (100 nM), please explain.

• Line 172 – ANOVA and t-test assumes that the data fit a normal distribution, include the test of normality to ensure appropriate statistics were used.

• Line 184 – Title says “similar activation marker expression by TCR-stimulated blood and liver MAITs”. Line 202 also says “equivalent upregulation of Cd69 and 4-1BB “. However, no statistical comparisons between blood and ld-MAITS are shown for CD69/ 4-1BB expression following TCR activation (Figure 1C).

• Line 191 – CD69 expression following 5-A-RU is not significantly different compared to untreated (Figure 1C), the statement should be changed to increased CD69 expression was observed with E.coli stimulation compared to untreated.

• Line 192 – indicate p values in Figure 1C for comparison of E.coli vs. 5-A-RU CD69 expression.

Minor comments:
- Line 18 – typo, add invariant to MAIT abbreviation.
- Line 48 – no need to abbreviate APCs again, abbreviated in line 37.
- Line 94- how many PBMCs or LDMCs cells were treated?
- Line 119 – add blood MAITs were flow sorted as CD8+ CD161+ Vα7.2+ as mentioned previously (ref. 22)
- Line 210 – can you add any statistics to pie chart using SPICE software or mention p values comparing poly-functional response of ld MAITs and blood MAITs using prism.
- Line 250- when cells are being stimulated you can use “unstimulated” control instead of “untreated”.
- Line 279 – referring to Figure 5D is mistake, correct it to Figure 4D.
- Line 304– Have you tested IL-17A expression by ld-MAITs following TCR and cytokine stimulation using flow cytometry?
- Line 309- Ld-MAIT cells may have CD4+ subset, how many genes were contributed by this subset and can you substract it from data to compare DEGs from CD8+ MAITs in both blood and liver.
- Figure 1H – put p value or ns in graph comparing CD40L expression following cytokine stimulation in blood vs. liver.
- Figure 3 legend – add ns shows non-significant comparison, or mention p values for ns for consistency. MFI is not there in figure, delete it.
- Figure 4 legend- add information on how many donors were tested and Data is pooled from how many experiments. How many MAIT cells were flow sorted for RNA sequencing?

Response to questions asked was satisfactory.