Jawless vertebrates Agnatha (, Ancient Greek 'without jaws') is an infraphylum of jawless fish in the phylum Chordata, subphylum Vertebrata, consisting of both present (cyclostomes) and extinct ( conodonts and ostracoderms) species. Among recent animals, cyclosto ...

, which today consist entirely of lampreys and hagfish, have an

adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

similar to that found in jawed vertebrates. The cells of the agnathan AIS have roles roughly equivalent to those of

B-cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

and

T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

, with three

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

lineages identified so far: *VLRA (most similar to α/β T cells, in its role and pathway of differentiation) *VLRB (most similar to

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s) *VLRC (most similar to γ/δ T cells) VLRA and VLRB were identified in 2009, while VLRC was discovered in 2013. Instead of immunoglobulins, they use variable lymphocyte receptors.

Antigen receptors

Jawless vertebrates do not have immunoglobulins (Igs), the key

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s to B-cells and T-cells. However, they do possess a system of

leucine-rich repeat A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats common ...

(LRR) proteins that make up variable lymphocyte receptors (VLRs). This system can produce roughly the same number of potential receptors that the Ig-based system found in jawed vertebrates can. Instead of recombination-activating genes (RAGs),

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s coding for VLRs can be altered by a family of

cytidine deaminase Cytidine deaminase is an enzyme that in humans is encoded by the ''CDA'' gene. This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytid ...

s known as APOBEC, possibly through gene conversion. Cytidine deaminase 1 is associated with the assembly of VLRA and VLRC and cytidine deaminase 2 appears to assemble VLRB.

Evolution

The gene expression profiles of lymphocyte-like cells (LLCs) in jawless vertebrates indicate that VLRB⁺ LLCs and B cells share a common ancestor, and VLRA⁺ and VLRC⁺ LLCs and T cells share a common ancestor. Like B cells and T cells, the development of VLRB⁺ LLCs is spatially separated from the development of VLRA⁺ and VLRC⁺ LLCs. VLRB⁺ LLCs and B cells develop in hematopoietic tissues: VLRB⁺ LLCs develop in the typhlosole and kidneys and B cells develop in bone marrow. VLRA⁺ and VLRC⁺ LLCs develop in a thymus-like organ called the thymoid, similar to T cells developing in the thymus. VLRB molecules and B cells can directly bind to antigens and VLRB-transfected cells secrete VLRB protein products, similar to B cells in jawed vertebrates. VLRA⁺ LLCs were unable to bind ''Bacillus anthracis'', ''Escherichia coli'', ''Salmonella typhimurium'', or ''Streptococcus pneumoniae'' before or after immunization, suggesting that VLRAs require antigen processing like TCRs. However, MHCs or MHC-like molecules that could present processed antigens have not been found in lampreys, and some VLRAs expressed in yeast were able to directly bind to antigens. The antigen binding of VLRCs has not been studied. However, the VLRC gene is close in proximity and sequence to the VLRA gene and the two are often co-expressed in LLCs, suggesting that both are TCR-like receptors.

Antigen receptors

Evolution

References

Further reading