Evolution of innate-like T cells and their selection by MHC class I-like molecules

Abstract

Until recently, major histocompatibility complex (MHC) class I-like-restricted innate-like αβT (iT) cells expressing an invariant or semi-invariant T cell receptor (TCR) repertoire were thought to be a recent evolutionary acquisition restricted to mammals. However, molecular and functional studies in Xenopus laevis have demonstrated that iT cells, defined as MHC class I-like-restricted innate-like αβT cells with a semi-invariant TCR, are evolutionarily conserved and prominent from early development in amphibians. As these iT cells lack the specificity conferred by conventional αβ TCRs, it is generally considered that they are specialized to recognize conserved antigens equivalent to pathogen-associated molecular patterns. Thus, one advantage offered by the MHC class I-like iT cell-based recognition system is that it can be adapted to a common pathogen and function on the basis of a relatively small number of T cells. Although iT cells have only been functionally described in mammals and amphibians, the identification of non-classical MHC/MHC class I-like genes in other groups of endothermic and ectothermic vertebrates suggests that iT cells have a broader phylogenetic distribution than previously envisioned. In this review, we discuss the possible role of iT cells during the emergence of the jawed vertebrate adaptive immune system.

Keywords: Amphibians; Comparative immunology; Evolution; MHC class I-like; Unconventional T cells; XNC; iT cells.

Fig. 1

Tissue-specific expression of invariant TCRα rearrangements in pre-metamorphic stage 50–53 (~2 weeks of age) tadpoles. Gene expression of iVα6-Jα1.43, iVα22-Jα1.32, iVα40-Jα1.22, iVα41-Jα1.40, iVα45-Jα1.14, and iVα23-Jα1.1.3 in the thymus, kidney, intestine, liver, skin, and gill is shown. Results are normalized to an endogenous control and presented as fold change in expression compared with the lowest observed expression. Data are presented as mean ± SE (n = 4); nd below detection level. All animals were from the X. laevis Research Resource for Immunology at the University of Rochester (http://www.urmc.rochester.edu/smd/mbi/xenopus/index.htm)

Fig. 2

Schematic representation of the X. laevis TCRα/δ locus on chromosome 1L. Vα (light blue) Vα utilized in invariant TCRα rearrangements (dark blue), Vδ (yellow), VHδ (light red), J (black), and three Cα (green) and three Cδ (orange) were numbered according to their position in the locus or, as in the case of Cα, to prior description. Transcriptional orientation is demonstrated by an arrow above each gene segment. Syntenic genes between the 1L and 1S are shown in white. Olfactory receptors (OR) are shown in gray. For Vα segments on 1S and scaffold 131, the percent amino acid identity to the closest V relation on 1L is denoted above the respective gene (Color figure online)

Fig. 3

Schematic representation of the X. laevis TCRα genes identified on chromosome 1S (a) and scaffold 131 (b). Vα (light blue), J (black), and Cα (green). Transcriptional orientation is indicated by an arrow above each gene segment. Syntenic genes between the 1L and SL are shown in white. Gap in sequence is denoted by dashed boxes. For Vα segments, the percent amino acid identity to the closest Vrelation on 1L is denoted above the respective gene (Color figure online)

Fig. 4

Summary of the currently known distribution of MHC class Ia, MHC class I-like, CD1, MR1, γδ T, αβT, and iT cells across jawed vertebrate taxa. Note that iT cells are defined as MHC class I-like-restricted αβT cells with a semi-invariant TCR. MYA: millions years ago