Abstract
The study of immune related genes in lampreys and hagfish provides a unique perspective on the evolutionary genetic underpinnings of adaptive immunity and the evolution of vertebrate genomes. Separated from their jawed cousins at the stem of the vertebrate lineage, these jawless vertebrates have many of the gene families and gene regulatory networks associated with the defining morphological and physiological features of vertebrates. These include genes vital for innate immunity, inflammation, wound healing, protein degradation, and the development, signaling and trafficking of lymphocytes. Jawless vertebrates recognize antigen by using leucine-rich repeat (LRR) based variable lymphocyte receptors (VLRs), which are very different from the immunoglobulin (Ig) based T cell receptor (TCR) and B cell receptor (BCR) used for antigen recognition by jawed vertebrates. The somatically constructed VLR genes are expressed in monoallelic fashion by T-like and B-like lymphocytes. Jawless and jawed vertebrates thus share many of the genes that provide the molecular infrastructure and physiological context for adaptive immune responses, yet use entirely different genes and mechanisms of combinatorial assembly to generate diverse repertoires of antigen recognition receptors.
Highlights
All metazoans utilize germline-encoded pattern recognition receptors for detection of pathogens and initiation of innate immune responses [1, 2]
The genes encoding the key recognition receptors of this adaptive immune system, Ig, T cell receptor (TCR) and major histocompatibility complex (MHC) genes, are present in all jawed vertebrates, yet none of them have been found in agnathans
Two AIDAPOBEC family member genes, CDA1 and CDA2, have been found in lamprey, and they are postulated to catalyze the assembly of variable lymphocyte receptors (VLRs) genes by a gene conversion-like mechanism that results in a potential antigen receptor repertoire of >1014 antigen specificities [7, 11]
Summary
All metazoans utilize germline-encoded pattern recognition receptors for detection of pathogens and initiation of innate immune responses [1, 2]. In gnathostomes (jawed vertebrates), T and B lymphocytes use the somatically diversified T cell receptor (TCR) and immunoglobulin (Ig) genes, respectively, for adaptive immune responses. During their development in the thymus and hematopoietic tissues, respectively, T and B lymphocytes use V(D)J recombination to generate diverse repertoires of their Ig-based antigen receptors that are capable of recognizing >1014 potential antigens. Gnathostomes construct Ig and TCR antigen receptors from IgSF domains; in this lineage RAG1 and RAG2 are vital for gene assembly and AID for somatic hypermutation, class switching, and gene conversion. Immune competence, genes that facilitate immune function, and the unique features of the adaptive immune system in jawless vertebrates
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