Do lampreys have lymphocytes? The Spi evidence.

Shintani S, Terzic J, Sato A, Saraga-Babic M, O'hUigin C, Tichy H, Klein J.

Proc Natl Acad Sci U S A 2000 Jun 20;97(13):7417-22



The immune response of vertebrates has two arms, the adaptive and the nonadaptive (1). The adaptive response is effected by lymphocytes that express antigen-specific receptors on their surfaces, either the B cell (Ig) or the T cell receptors. The latter recognize peptides presented to them by molecules encoded in the MHC genes. Ig, T cell receptors, and MHC molecules are known only from jawed vertebrates (Gnathostomata); all efforts to isolate them or clone the encoding genes in jawless vertebrates (Agnatha), the lampreys and the hagfish, have failed (2). On the strength of this negative evidence, it is generally accepted that jawless vertebrates lack an adaptive immune system…………….


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Primitive synteny of vertebrate major histocompatibility complex class I and class II genes.
Ohta Y, Okamura K, McKinney EC, Bartl S, Hashimoto K, Flajnik MF. Proc Natl Acad Sci U S A 2000 Apr 25;97(9):4712-7

Major histocompatibility complex (MHC) class I and class II molecules bind to and display peptidic antigens acquired from pathogens that are recognized by lymphocytes coordinating and executing adaptive immune responses. The two classes of MHC proteins have nearly identical tertiary structures and were derived from a common ancestor that probably existed not long before the emergence of the cartilaginous fish. Class I and class II genes are genetically linked in tetrapods but are not syntenic in teleost fish, a phylogenetic taxon derived from the oldest vertebrate ancestor examined to date. Cartilaginous fish (sharks, skates, and rays) are in the oldest taxon of extant jawed vertebrates; we have carried out segregation analyses in two families of nurse sharks and one family of the banded houndshark that revealed a close linkage of class IIalpha and beta genes both with each other and with the classical class I (class Ia) gene. These results strongly suggest that the primordial duplication giving rise to classical class I and class II occurred in cis, and the close linkage between these two classes of genes has been maintained for at least 460 million years in representatives of most vertebrate taxa.

Abstract:  [link to the full-text article from this page]


Major histocompatibility complex (MHC) class I and class II molecules function to display foreign peptides to T cells and are thus fundamental components of the adaptive immune system (reviewed in ref. 1). Class I and class II proteins are composed of four extracellular domains, with two membrane-proximal domains belonging to the Ig superfamily, and two membrane-distal domains that form the peptide-binding region (PBR) (2, 3). The PBR/peptide complex is recognized by T cells via their T cell receptors, leading to induction of acquired immunity. Class II molecules are composed of MHC-encoded alpha  and beta  chains, each having two extracellular domains (half of the PBR and one Ig domain) whereas MHC-encoded class I heavy chains are constituted of three domains encompassing the entire PBR and one Ig domain [the noncovalently associated beta 2-microglobulin contributes the other Ig domain of class I molecules; its gene was probably translocated out of the MHC early in vertebrate evolution (4)]. Class I and class II genes are very polymorphic in most species, and PBR amino acid residues that interact with peptides are under Darwinian positive selection (5, 6). Class I molecules are expressed ubiquitously and associate with peptides generated in the cytosol by the multicatalytic proteasome whereas class II proteins bind to lysosomally generated peptides and are expressed only by B cells, antigen presenting cells, and the thymus (reviewed in ref. 1). In addition to the classical class I, or class Ia, genes described above, there are also nonclassical, or class Ib, genes whose products are structurally similar to class Ia but are generally nonpolymorphic, may or may not be MHC-linked, and can bind to molecules besides peptides (7). There is universal agreement that class I and class II genes are derived from a common ancestor, believed by most investigators, but not all (8), to be class II-like (9-11).

Class I and class II genes have been isolated from representatives of almost all major jawed vertebrate taxa, including cartilaginous fish, bony fish, amphibians, birds, and mammals (reviewed in refs. 12 and 13). Interestingly, there has been no hint of their presence (or the existence of any other defining component of the adaptive immune system) in jawless fish or invertebrates, suggesting that the MHC arose rather abruptly in a jawed vertebrate ancestor, probably a placoderm (14). One hypothesis suggests that genome-wide duplications played a role in the emergence of the MHC and the entire adaptive immune system (15), as genes linked to class I and class II are found in four paralogous clusters in mammalian genomes (16, 17). In all tetrapod species examined to date, including several mammals, the bird Gallus (18), and the amphibian Xenopus (13, 19), class I and class II genes are closely linked. However, among older taxa, all investigated bony fish species, including the zebrafish (20), carp, salmon (21), and trout (22), the presumed classical class I and class II genes are not linked and even are found on different chromosomes. It was proposed that one of two scenarios occurred in vertebrate evolution (20, 23): (i) class I and class II genes arose on different paralogous chromosomes (likely the ones mentioned above) in a jawed vertebrate ancestor and "clustered" together in a tetrapod ancestor, or (ii) the genes were originally in the same linkage group but were rent apart in a recent teleost ancestor and now lie on different chromosomes in this single vertebrate lineage. The two scenarios can be distinguished with studies of cartilaginous fish, the oldest class of extant jawed vertebrates (24). Thus, to examine the primordial condition of the MHC regarding class Ia/class II linkage, we carried out family studies in members of two divergent orders of sharks separated by over 100 million years (24).

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Here is a summary from the chapter 7 "Evolution of the adaptive immune system" in the book "Introductory Immunobiology" by Huw Davies [London: Chapman & Hall, 1997, pp.224-256]

Fishes are the first vertebrates to appear on the fossil record. The immune system of the fishes is likely to resemble that of the earliest vertebrates. The immune system of the Agnatha is the most primitive among the vertebrates (they don't have a pol;ymorphic MHC, they don't recognize non-self moplecules -no allorecognition-, no thymus, no T-cell repertoire). The antibody-dependent (classical) pathway of complement is also absent from lampreys, hagfish and some cartilaginous fish. The alternative complement pathway of the immune system, however, exists even in the Agnatha. The alternative pathway may have acted in the earliest vertebrates as a source of opsonins and other inflammatory molecules. All jawed vertebrates possess both classical and alternative complement activation pathways, a true thymus and true secondary lymphoid tissues for collecting and presenting antigens to lymphocytes. Cartliginous fish are the most primitive class of vertebrates shown to have an adaptive immune system. Jawed fishes also have diffuse lymphoid tissue associated with the digestive tract. Immunoglobulins are present in all fishes (but only IgM isotype). It is only the teleosts who have the memory reaction -immunoglobulin response to recall antigens-. Class I and class II MHC genes exist in sharks and rays and teleosts. Strong graft rejection (mediated by the MHC) is only seen in teleosts. MHC does not exist in the Agnatha.