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Proc Natl Acad Sci U S A. 2016 May 24;113(21):E2983-92. doi: 10.1073/pnas.1600674113. Epub 2016 May 11.

Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals.

Author information

1
Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, 78352 Jouy-en-Josas, France; pierre.boudinot@jouy.inra.fr olivier.lantz@curie.fr.
2
INSERM U932, Institut Curie, Paris Sciences et Lettres Research University, 75005 Paris, France;
3
Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, 78352 Jouy-en-Josas, France;
4
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
5
The International ImMunoGeneTics Information System (IMGT), Institut de Génétique Humaine, Unité Propre de Recherche CNRS 1142, Université de Montpellier, 34396 Montpellier Cedex 5, France;
6
INSERM U932, Institut Curie, Paris Sciences et Lettres Research University, 75005 Paris, France; Center of Clinical Investigation in Biotherapy 1428, Gustave-Roussy/Curie, 75005 Paris, France; Laboratoire d'Immunologie Clinique, Institut Curie, Paris 75005, France pierre.boudinot@jouy.inra.fr olivier.lantz@curie.fr.

Abstract

Whereas major histocompatibility class-1 (MH1) proteins present peptides to T cells displaying a large T-cell receptor (TR) repertoire, MH1Like proteins, such as CD1D and MR1, present glycolipids and microbial riboflavin precursor derivatives, respectively, to T cells expressing invariant TR-α (iTRA) chains. The groove of such MH1Like, as well as iTRA chains used by mucosal-associated invariant T (MAIT) and natural killer T (NKT) cells, respectively, may result from a coevolution under particular selection pressures. Herein, we investigated the evolutionary patterns of the iTRA of MAIT and NKT cells and restricting MH1Like proteins: MR1 appeared 170 Mya and is highly conserved across mammals, evolving more slowly than other MH1Like. It has been pseudogenized or independently lost three times in carnivores, the armadillo, and lagomorphs. The corresponding TRAV1 gene also evolved slowly and harbors highly conserved complementarity determining regions 1 and 2. TRAV1 is absent exclusively from species in which MR1 is lacking, suggesting that its loss released the purifying selection on MR1. In the rabbit, which has very few NKT and no MAIT cells, a previously unrecognized iTRA was identified by sequencing leukocyte RNA. This iTRA uses TRAV41, which is highly conserved across several groups of mammals. A rabbit MH1Like gene was found that appeared with mammals and is highly conserved. It was independently lost in a few groups in which MR1 is present, like primates and Muridae, illustrating compensatory emergences of new MH1Like/Invariant T-cell combinations during evolution. Deciphering their role is warranted to search similar effector functions in humans.

KEYWORDS:

MAIT; MHC; TCR; evolution; mammals

PMID:
27170188
PMCID:
PMC4889381
DOI:
10.1073/pnas.1600674113
[Indexed for MEDLINE]
Free PMC Article

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