Evolution of Alternative Adaptive Immune Systems in Vertebrates

Abstract

Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucine-rich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion-like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases. B-like cells develop in the hematopoietic typhlosole and kidneys, whereas T-like cells develop in the thymoid, a thymus-equivalent region at the gill fold tips. Thus, the dichotomy between T-like and B-like cells and the presence of dedicated lymphopoietic tissues emerge as ancestral vertebrate features, whereas the somatic diversification of structurally distinct antigen receptor genes evolved independently in jawless and jawed vertebrates.

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

“…We have recently reported that the sea lamprey, Petromyzon marinus, generates a broad repertoire of anti-glycan antibodies in response to immunization with a variety of cell lines and biological tissues (McKitrick et al, in review). In contrast to the gnathostomes which produce antibodies made of immunoglobulin domains, the agnathans or jawless vertebrates, utilize a class of proteins constructed with leucine rich repeat motifs called Variable Lymphocyte Receptors (VLRs) as antigen receptors (Pancer et al, 2004;Alder et al, 2005Alder et al, , 2008Boehm et al, 2018). These single-chain antibodies are produced and secreted by the VLRB lymphocyte lineage, and several groups have discovered and characterized monoclonal VLRB proteins that are specific for distinct carbohydrate structures (Han et al, 2008;Hong et al, 2013;Luo et al, 2013;Collins et al, 2017).…”

Rethinking Thymic Tolerance: Lessons from Mice

“…The thymus produces multiple T cell types that play key roles in both innate and adaptive immune responses. The importance of these responses has now been shown in sister lineages of vertebrates, long after the function of the thymus was proven for jawed vertebrates in the 1960s [1,2]. Indeed, a key feature of adaptive immunity lies in its ability to generate a wide diversity of antigen receptors that target non-self.…”

Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance

“…Even jawless fish such as lamprey have structures resembling a thymus and their genome encodes for various immune‐effector genes (eg, cytokines, relevant transcription factors) . While lymphocytes of jawless fish express variable lymphocyte receptors, somatically diversified antigen receptors composed of tandem arrays of leucine‐rich repeats, adaptive T and B cells equipped with antigen receptors generated by recombination of receptor gene elements first appear in jawed vertebrates . Since ILCs do not depend on recombined antigen receptors, it has been speculated that they are an evolutionary older branch of the lymphocyte family.…”