Abstract
Mucosal-associated invariant T (MAIT) cells are a subpopulation of evolutionarily conserved innate-like T lymphocytes bearing invariant or semi-invariant TCRα chains paired with a biased usage of TCRβ chains and restricted by highly conserved monomorphic MHC class I-like molecule, MR1. Consistent with their phylogenetically conserved characteristics, MAIT cells have been implicated in host immune responses to microbial infections and non-infectious diseases, such as tuberculosis, typhoid fever, and multiple sclerosis. To date, MAIT cells have been identified in humans, mice, cows, sheep, and several non-human primates, but not in pigs. Here, we cloned porcine MAIT (pMAIT) TCRα sequences from PBMC cDNA, and then analyzed the TCRβ usage of pMAIT cells expressing the TRAV1-TRAJ33 chain, finding that pMAIT cells use a limited array of TCRβ chains (predominantly TRBV20S and TRBV29S). We estimated the frequency of TRAV1-TRAJ33 transcripts in peripheral blood and tissues, demonstrating that TRAV1-TRAJ33 transcripts are expressed in all tested tissues. Analysis of the expression of TRAV1-TRAJ33 transcripts in three T-cell subpopulations from peripheral blood and tissues showed that TRAV1-TRAJ33 transcripts can be expressed by CD4+CD8−, CD8+CD4−, and CD4−CD8− T cells. Using a single-cell PCR assay, we demonstrated that pMAIT cells with the TRAV1-TRAJ33 chain express cell surface markers IL-18Rα, IL-7Rα, CCR9, CCR5, and/or CXCR6, and transcription factors PLZF, and T-bet and/or RORγt. In conclusion, pMAIT cells expressing the TRAV1-TRAJ33 chain have characteristics similar to human and mouse MAIT cells, further supporting the idea that the pig is an animal model for investigating MAIT cell functions in human disease.
Highlights
T lymphocytes, consisting of conventional and unconventional T cells, play vital roles in immune responses
Invariant natural killer T cells, the extensively studied innate-like T cells with an effector-memory phenotype [6], express an invariant TCR TRAV10-TRAJ18 chain in humans (TRAV11-TRAJ18 in mice and TRAV10-TRAJ18 in pigs) with a CDR3 of a constant length [7,8,9,10], and recognize self-lipids or microbe-derived lipids presented by the non-polymorphic MHCIb molecule, CD1d [11, 12]
Other pTRAV1-TRAJ33 transcripts with different CDR3α sequences (11%), and some out-of-frame sequences (18%) were obtained from these PCR products. These results suggest that porcine T cells express the orthologous TCR Vα-Jα transcripts of the human or mouse Mucosal-associated invariant T (MAIT) invariant TCRα chain, indicating MAIT cells are present in pigs, and these transcripts contain a conserved canonical CDR3α sequence, some non-canonical sequences were observed
Summary
T lymphocytes, consisting of conventional and unconventional T cells, play vital roles in immune responses. Invariant natural killer T (iNKT) cells, the extensively studied innate-like T cells with an effector-memory phenotype [6], express an invariant TCR TRAV10-TRAJ18 chain in humans (TRAV11-TRAJ18 in mice and TRAV10-TRAJ18 in pigs) with a CDR3 of a constant length [7,8,9,10], and recognize self-lipids or microbe-derived lipids presented by the non-polymorphic MHCIb molecule, CD1d [11, 12]. It has been reported that genes encoding the two evolutionarily conserved proteins, the invariant TCRα chain and MR1, coevolved in mammals [31], implying an important role for MAIT cells in the host immune response that has been evolutionarily maintained. Our study demonstrated that MAIT cells are present in pigs and have similar phenotypes to human and mouse MAIT cells
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