The genes of the major histocompatibility complex were first known for the part they played in transplant rejection. Recently, however, it has become clear that the products of that region have an important part to play in the control of the immune response, through their effects both on cooperative and on aggressive interactions between cells. It is now possible to guess at the mechanisms which may underly the association of some major histocompatibility antigens with disease.

Products of the major histocompatibility complex and their relationship to the immune response

SUMMARY

NH2, terminal amino acid sequence determinations of clawed toad (Xenopus laevis) immunoglobulins indicate that approximately 30% of the heavy chains and less than 5% of the light chains have unblocked NH2 termini. The major amino acid sequence of the X. laevis 7S immunoglobulin heavy chains is the same as that of the 19S immunoglobulin heavy chains. Thus in the synthesis of the heavy chains, the VH genes coding for unblocked heavy chains can associate with CH genes of both the 19S and 7S classes. This association is particularly important in amphibians because, in contrast to mammals and birds, the majority of amphibian antibody-producing cells synthesize both 19S and 7S immunoglobulins and do not participate in the ‘genetic switch’ characteristic of lymphocyte differentiation in higher organisms. In X. laevis, the major amino acid sequence at the first twenty-four positions of the unblocked heavy chains shows approximately 54% difference from the prototype amino acid sequence of the mammalian VHIII subgroup. Thus, the VHIII gene(s) must have started to appear after the evolutionary divergence of the common ancestor of mammals and birds from the amphibian line. The amino acid composition of the X. laevis 7S immunoglobulin heavy chains differs from that of its 19S immunoglobulins as well as those of human IgG and IgA. These data support the concepts (a) that amphibian 7S and 19S immunoglobins belong to distinct classes and (b) that amphibian 7S immunoglobulin does not resemble mammalian IgG or IgA.

Immunoglobulin evolution: chemical study of clawed toad (Xenopus laevis) heavy and light chains.

The subclass heterogeneity of pig IgG.

Comparative analyses of protein structure in different species can be useful guides to developments in evolutionary history (Arnheim, 1973). This approach is as applicable to the field of immunochemistry as it is to any other biological discipline. Such an analysis involves a search for clues to the origins and developmental processes of a currently extant biological system, e.g., the humoral immune response, by an examination of various aspects of the system as they exist in contemporary representatives of various phylogenetic levels of the animal kingdom. Such an approach assumes that current representatives of older phylogenetic categories are, in fact, reliable indicators of the nature of the particular functions as they existed millions of years ago. The validity of this assumption is perhaps never completely provable, but is nonetheless widely regarded as reasonable. Often, this assumption is the only basis on which certain inferences concerning evolutionary history can be made.

The Phylogenetic Origins of Immunoglobulin Structure

3 – Immunoglobulins III. Comparative Biochemistry and Evolution

Pig gamma-chains contain a significant fraction of the unblocked VHIII variable region subgroup. The amino terminal sequence (30 residues) was found to be uniform and more than 90% homologous with the prototype sequence of the human VHIII subgroup. An additional VHIII phylogenetically associated residue, glutamic acid in position 2 was identified in these porcine heavy chains.

Franĕk F

Papers

The amino-terminal sequence of the VHIII subgroup of pooled porcine IgG.