The MHC Molecules of Nonmammalian Vertebrates

Abstract

There is very little known about the long-term evolution of the MHC and MHC-like molecules. This is because both the theory (the evolutionary questions and models) and the practice (the animals systems, functional assays and reagents to identify and characterize these molecules) have been difficult to develop. There is no molecular evidence yet to decide whether vertebrate immune systems (and particularly the MHC molecules) are evolutionarily related to invertebrate allorecognition systems, and the functional evidence can be interpreted either way. Even among the vertebrates, there is great heterogeneity in the quality and quantity of the immune response. The functional evidence for T-lymphocyte function in jawless and cartilagenous fish is poor, while the bony fish seem to have many characteristics of a mammalian immune system. The organization and sequence of fish Ig genes also indicate that important events in the evolution of the immune system and the MHC occurred in the fish, but thus far there is no molecular evidence for recognizable MHC-like molecules in any fish. There is clearly an MHC in amphibians and birds with many characteristics like the MHC of mammals (a single genetic region encoding polymorphic class I and class II molecules) and evidence for polymorphic class I and class II molecules in reptiles. However, many details differ from the mammals, and it is not clear whether these reflect historical accident or selection for different lifestyles or environment. For example, the adult frog Xenopus has a vigorous immune system with many similarities to mammals, a ubiquitous class I molecule, but a much wider class II tissue distribution than human, mouse and chicken. The Xenopus tadpole has a much more restricted immune response, no cell surface class I molecules and a mammalian class II distribution. The axolotl has a very poor immune response (as though there are no helper T cells), a wide class II distribution and, for most animals, no cell surface class I molecule. It would be enlightening to understand both the mechanisms for the regulation of the MHC molecules during ontogeny and the consequences for the immune system and survival of the animals. These animals also differ markedly in the level of MHC polymorphism. Another difference from mammals is the presence of previously uncharacterized molecules. In Xenopus and reptiles, there are two populations of class I alpha chain on the surface of erythrocytes, those in association with beta 2m and those in association with a disulfide-linked homodimer.(ABSTRACT TRUNCATED AT 400 WORDS)

MHC Class II Pseudogene and Genomic Signature of a 32-kb Cosmid in the House Finch (Carpodacus mexicanus)

“…Chickens have provided particularly powerful models for implicating Mhc genes in resistance to infectious disease (Briles and McGibbon 1948;Schat et al 1994;Kaufman and Salamonsen 1997). Structurally, the coding regions of avian Mhc genes have many similarities to those of other vertebrates with both class I genes responsible for immune responses to intracellular parasites and class II genes that bind extracellular parasites (Kaufman et al 1990;Shiina et al 1999b). The chicken Mhc is also known to possess class III Mhc genes such as factor B that are involved in the complement system of the cellular immune response (Nonaka et al 1994).…”

Evolution of the major histocompatibility complex: isolation of class II A cDNA clones from the cartilaginous fish.

“…Was an ancestral MHC molecule class I-like or class II-like? These questions, which are of fundamental importance in understanding the evolution of immunity (6)(7)(8), can be addressed only by studying MHC genes of primitive creatures. In addition, the structure of such MHC genes might provide a clue to the origin of membrane-distal, peptide-binding domains (9) and to the primordial function of MHC molecules.…”

Size polymorphism of chicken major histocompatibility complex-encoded B-G molecules is due to length variation in the cytoplasmic heptad repeat region.

“…The biological functions of these molecules are unknown, but the serologically polymorphic ones may have some role in specific recognition of foreign antigens by cells of the immune system (4,6), based on the high polymorphism, location in the MHC, distinctive tissue distribution, and two interesting phenomena: polymorphic B-G epitopes are recognized by so-called "natural antibodies" in a variety of species (7,8) and B-G molecules are responsible for the "adjuvant effect" for humoral responses to other molecules on erythrocytes and in liposomes (refs. 9 and 10; J.S., H.…”