In Situ Detection of MAIT Cells and MR1-Expressing Cells in Tissue Biopsies Utilizing Immunohistochemistry
The mucosa-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial vitamin B2 metabolites presented via MR1, a MHC-I-related protein. MAIT cells are abundant in blood and mucosa, where they display a broad range of functions. Spatial distribution of cells and their proximity to other cells, including infected cells and antigen presenting cells, are crucial components of cell-mediated immunity. Here we describe techniques to detect MAIT cells and MR1-expressing cells in situ, which enable the visualization, distribution, and localization of these cells within their histological context. We provide specific protocols and describe potential advantages and limitations for each of the presented methodologies for studying MAIT cells in human tissues.
Key wordsMAIT cells MR1 In situ detection Immunohistochemistry Immunofluorescence Fixation Antibodies and microscopy
This work was supported by grants to A.G. from Swedish Physicians against AIDS Foundation, the Swedish Society of Medicine, Tore Nilsons Research Foundation for Medical Research, and the Sigurd and Elsa Goljes Memorial Fund. J.K.S. was supported by grants from the Swedish Research Council (2016-03052), the Swedish Cancer Society (CAN 2017/777), the Swedish Heart-Lung Foundation (20180675), and the US National Institutes of Health (R01DK108350). A.T. was supported by grants from the Clas Groschinsky Minnesfond, Magnus Bergvalls Stiftelse, and the Swedish Society of Medicine.
- 9.Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Chen Z, Eckle SB, Uldrich AP, Birkinshaw RW, Patel O, Kostenko L, Meehan B, Kedzierska K, Liu L, Fairlie DP, Hansen TH, Godfrey DI, Rossjohn J, McCluskey J, Kjer-Nielsen L (2013) Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J Exp Med 210:2305–2320CrossRefGoogle Scholar
- 12.Gibbs A, Leeansyah E, Introini A, Paquin-Proulx D, Hasselrot K, Andersson E, Broliden K, Sandberg JK, Tjernlund A (2017) MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation. Mucosal Immunol 10:35–45CrossRefGoogle Scholar
- 13.Sobkowiak MJ, Davanian H, Heymann R, Gibbs A, Emgard J, Dias J, Aleman S, Kruger-Weiner C, Moll M, Tjernlund A, Leeansyah E, Sallberg Chen M, Sandberg JK (2019) Tissue-resident MAIT cell populations in human oral mucosa exhibit an activated profile and produce IL-17. Eur J Immunol 49:133–143CrossRefGoogle Scholar
- 14.Gibbs A, Buggert M, Edfeldt G, Ranefall P, Introini A, Cheuk S, Martini E, Eidsmo L, Ball TB, Kimani J, Kaul R, Karlsson AC, Wahlby C, Broliden K, Tjernlund A (2018) Human immunodeficiency virus-infected women have high numbers of CD103−CD8+ T cells residing close to the basal membrane of the ectocervical epithelium. J Infect Dis 218:453–465CrossRefGoogle Scholar