Publisher Summary This chapter provides information on histocompatibility-linked immune response genes. The genetic study of the capacity to form specific immune responses has revealed that the recognition of antigens as immunogens by individual animals and inbred strains is governed by the product of individual dominant genes located in the genome in close relationship with the genes coding for the molecules bearing the major histocompatibility specificities. These genes are termed as “histocompatibility,” or “H-linked Ir genes.” The presence of relevant genes permit immune responses to be formed, characterized by cellular immunity and antibody synthesis against the determinants on the antigens concerned. Three types of antigens are most useful in the identification of H-linked Ir genes: (1) synthetic polypeptides with limited structural heterogeneity; (2) alloantigens that differ slightly from their autologous counterparts, and (3) complex multideterminants antigens administered in limiting immunizing doses in conditions where only the most immunogenic determinants are recognized. Thus, the discovery of specific H-linked Ir genes depends upon experiments wherein the immunological system is presented with a challenge of highly restricted heterogeneity and specificity. The chapter presents a description of the specific immune responses that are under the control of H-linked Ir genes in guinea pigs, mice, and rats.

https://science.sciencemag.org/content/sci/175/4019/273.full.pdf

Histocompatibility-Linked Immune Response Genes

Diversity in the CDR3 Region of VH Is Sufficient for Most Antibody Specificities

An amino acid sequence analysis of the N-terminal immunoglobulin heavy and light chain variable regions (VH and VL) from 16 hybridoma proteins which bind phosphorylcholine as well as the complete sequence analysis of 9 of these VH regions is presented. There seem to be more VH regions participating in the phosphorylcholine response than can be encoded directly by germ-line VH gene segments. Moreover, the V regions from IgG antibodies are considerably more variable than those from their IgM counterparts. These observations raise the possibility that a somatic mechanism for V region diversification produces greater diversity in IgG than in IgM antibodies.

IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts.

https://www.cell.com/cell/pdf/0092-8674(78)90041-7.pdf

Sequences of mouse immunoglobulin light chain genes before and after somatic changes

Antibodies represent a complex eukaryotic system that has fascinated biologists for the past 75 years. The immune system has evolved novel and sophisticated strategies for dealing with extremely large amounts of information. These include strategies for information storage, information expression, and information evolution. Indeed, one of the driving forces in molecular immunology has been the attempt to formulate and analyze mechanisms responsible for the diversity of antibodies. Perhaps this consideration, more than any other, convinced many biologists that the immune system has evolved unique genetic strategies to protect the integrity of the vertebrate organism. We disagree with this viewpoint.

The Organization, Expression, and Evolution of Antibody Genes and Other Multigene Families

The immune response to dextran having the alpha-1,3 linkage may be under the control of antibody structural genes. Mice that respond well to this antigen produce antibody restricted with respect to light chain class (lambda) and to an antigenic determinant resulting from a particular heavy and light chain interaction. The response to dextran is controlled by a locus linked to the-heavy chain locus.

https://science.sciencemag.org/content/sci/177/4044/178.full.pdf

William R. Geckeler

Papers

Genetics of the antibody response to dextran in mice.

First order considerations in analyzing the generator of diversity