Conservation of mucosal associated invariant T (MAIT) cells and the MR1 restriction element in ruminants, and abundance of MAIT cells in spleen

Abstract

MHC-related protein 1 (MR1) is a highly conserved MHC class I-like molecule. Human and murine mucosal associated invariant T (MAIT) cells are restricted by MR1 and express an invariant T cell receptor. Even though MR1 protein expression on the cell surface has not been demonstrated in vivo or ex vivo, it is assumed that MR1 presents a bacterial antigen from the intestinal lumen to MAIT cells because MAIT cells are present in the lamina propria and their expansion is dependent on the presence of intestinal micro flora. The existence of bovine MAIT cells and MR1 has been demonstrated recently although ovine MAIT cells and MR1 have not yet been described. We cloned bovine and ovine MR1 transcripts, including splice variants, and identified an anti human MR1 antibody that recognizes cells transfected with the bovine homolog. Using this antibody, no MR1 staining was detected using cells freshly isolated from blood, thymus, spleen, colon, ileum, and lymph node. MAIT cells are known to be enriched in the CD4/CD8 double negative peripheral blood T cell population, but their relative abundance in different tissues is not known. Comparison of the amount of MAIT cell-specific TCR transcript to the amount of constant α chain transcript revealed that numbers of MAIT cells are low in neonates and increase by 3-weeks of age. In 3-month old animals, MAIT cells are abundant in spleen and less so in ileum, peripheral blood, lymph node, colon, and thymus.

Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

“…The almostinvariant TCRa chain of MAIT cells is evolutionarily conserved in mammals 14,19 and results from a single Va-Ja rearrangement with a defined CDR3a length. In humans, some variation in the composition of the junction exists, suggesting a selective pressure operating at the protein level 14 .…”

Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells

“…The MAIT TCR ␣-chain contains a complementarity-determining region (CDR) 3 loop of constant length with two variable amino acids in the V-J junction (4) located at the base of this loop (10,11). MAIT cells are evolutionarily conserved in mammals with the canonical TCR ␣-chain composed of homologous TRAV and TRAJ elements also found in mice, cattle (5) and sheep (12). TRAV1-2 is not exclusive to MAIT cells, with some MHC-Irestricted T cells (13,14) and CD1b-restricted germline-encoded, mycolyl lipid-reactive (GEM) T cells also using this TRAV gene segment (15).…”

In Vitro and In Vivo Analysis of the Gram-Negative Bacteria–Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells

“…In contrast, mutagenesis experiments associated with structural studies identified crucial residues in the CDRs of the TCRa-chain that are required for Ag recognition by MAIT cells, regardless of Vb2 Jb usage (12). These residues are conserved in mammals (13,14). Although MAIT cell TCRs use preferential Vb segments, mutagenesis of individual residues within the CDRb regions indicates that the TCRb-chain of the MAIT cell TCRs did not play an important role in Ag reactivity, consistent with the lack of TCRb constraints (12,15).…”