Location, location, location: the evolutionary history of CD1 genes and the NKR-P1/ligand systems

Abstract

CD1 genes encode cell surface molecules that present lipid antigens to various kinds of T lymphocytes of the immune system. The structures of CD1 genes and molecules are like the major histocompatibility complex (MHC) class I system, the loading of antigen and the tissue distribution for CD1 molecules are like those in the class II system, and phylogenetic analyses place CD1 between class I and class II sequences, altogether leading to the notion that CD1 is a third ancient system of antigen presentation molecules. However, thus far, CD1 genes have only been described in mammals, birds and reptiles, leaving major questions as to their origin and evolution. In this review, we recount a little history of the field so far and then consider what has been learned about the structure and functional attributes of CD1 genes and molecules in marsupials, birds and reptiles. We describe the central conundrum of CD1 evolution, the genomic location of CD1 genes in the MHC and/or MHC paralogous regions in different animals, considering the three models of evolutionary history that have been proposed. We describe the natural killer (NK) receptors NKR-P1 and ligands, also found in different genomic locations for different animals. We discuss the consequence of these three models, one of which includes the repudiation of a guiding principle for the last 20 years, that two rounds of genome-wide duplication at the base of the vertebrates provided the extra MHC genes necessary for the emergence of adaptive immune system of jawed vertebrates.

Innate immune genes of the chicken MHC and related regions

“…The presence of the BNK-Blec gene pair was suggested as evidence that NKRP1-ligand gene pairs were originally in the MHC and translocated elsewhere during evolution (Rogers et al 2005 ). Interestingly, some passerine birds have the BNK-Blec gene pair on the Z chromosome (Ekblom et al 2011 ; Rogers and Kaufman 2016 ), so these genes may translocate with some facility, for reasons as yet unknown.…”

Mechanisms and Consequences of Antigen Presentation by CD1

“…The ancient origin of CD1, together with its evolutionary conservation among all mammalian species examined [9], suggests important functions of this antigen presentation system during an immune response. The number of CD1 genes in mammals differs widely among species, with some mammals expressing over ten CD1 genes.…”

Diversification of CD1 Molecules Shapes Lipid Antigen Selectivity

“…After the gene duplications that gave rise to ancestral MHC and CD1, vertebrate CD1 paralogs expanded through repeated duplication events ( Dascher 2007 ). This initial expansion was followed by differential pseudogenization and expansion of CD1 paralogs to various degrees across vertebrate species ( Rogers and Kaufman 2016 ). As such, CD1 gene content varies widely across vertebrates: primates have a single copy of the CD1A paralog, mice possess none, dogs encode six, and horses possess five ( Dascher 2007 ).…”