An Ancient, MHC-Linked, Nonclassical Class I Lineage in Cartilaginous Fish

• Published in: The Journal of immunology (1950) Vol. 204; no. 4; pp. 892 - 902
• Main Authors: Almeida, Tereza, Esteves, Pedro J, Flajnik, Martin F, Ohta, Yuko, Veríssimo, Ana
• Format: Journal Article
• Language: English
• Published: United States 15.02.2020
• Subjects: Adaptive Immunity - genetics; Amino Acid Sequence - genetics; Animals; Conserved Sequence - immunology; Gene Dosage; Genes, MHC Class I - genetics; Genes, MHC Class I - immunology; Phylogeny; Polymorphism, Genetic - immunology; Sharks - genetics; Sharks - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1901025

Cartilaginous fishes, or chondrichthyans, are the oldest jawed vertebrates that have an adaptive immune system based on the MHC and Ig superfamily-based AgR. In this basal group of jawed vertebrates, we identified a third nonclassical MHC class I lineage ( ), which is present in all species analyzed within the two major cartilaginous subclasses, Holocephali (chimaeras) and Elasmobranchii (sharks, skates, and rays). The deduced amino acid sequences of UDA have eight out of nine typically invariant residues that bind to the N and C termini of bound peptide found in most vertebrae classical class I (UAA); additionally, the other predicted 28 peptide-binding residues are perfectly conserved in all elasmobranch UDA sequences. is distinct from in its differential tissue distribution and its lower expression levels and is mono- or oligomorphic unlike the highly polymorphic has a low copy number in elasmobranchs but is multicopy in the holocephalan spotted ratfish ( ). Using a nurse shark ( ) family, we found that is MHC linked but separable by recombination from the tightly linked cluster of , , and genes, the so-called class I region found in most nonmammalian vertebrates. has predicted structural features that are similar to certain nonclassical class I genes in other vertebrates, and, unlike polymorpic classical class I, we anticipate that it may bind to a conserved set of specialized peptides.