ABSTRACT

The major histocompatibility complex (MHC) is a deoxyribonucleic acid (DNA) region that contains genes involved in antigen processing and presentation, though not exclusively. Evidence for MHC genes has been found in all jawed vertebrates studied, but not in jawless fish or invertebrates. Orthologous genes for the antigen presentation proteins, namely, class Ia/β-2-microglobulin (mhc1a/b2m) and class IIα/β (mhc2a/b), have been isolated in many cartilaginous fishes. The genes code for proteins with similar structures, levels of polymorphism, expression patterns, and linkage, though the number of loci appears reduced. Nonclassical class I genes (mhc1b), which have distinguishing features and functions, appear to exist in sharks as well. Two separate antigen-processing pathways provide the peptides that are ultimately loaded onto class I and class II molecules for presentation to 174T cells. Some of the components are MHC linked, namely, proteosome (psmb) and transporter (tap) subunits from the class I pathway and a chaperone (DM) from the class II pathway, and some are not, such as class II invariant chain (Ii). The shark MHC appears to contain at least one copy of mhc1a, mhc2a, mhc2b as well as two tap and two psmb genes, two genes for components of the complement system (c4 and cfb), and a brd2 gene, all genes that are MHC linked in most other vertebrates. Unique to the shark MHC is the presence of b2m, an ancient psmb8l gene, and two copies of cfb. Sharks have two other genes, cd74 and ciita (class II transactivator), that are important for class II protein function but are not MHC linked. Obviously missing from all fishes is DM, a nonclassical class II protein that serves as a chaperone in the class II antigen-processing pathway.