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

Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

https://www.pnas.org/content/pnas/92/25/11810.full.pdf

Human neoplasms elicit multiple specific immune responses in the autologous host.

Biology of the Mouse Histocompatibility-2 Complex

Heat shock proteins and the immune response

The major histocompatibility complex (MHC) has become a paradigm for how selection can act to maintain adaptively important genetic diversity in natural populations. Here, we review the contribution of studies on the MHC in non-model species to our understanding of how selection affects MHC diversity, emphasising how ecological and ethological processes influence the tempo and mode of evolution at the MHC, and conversely, how variability at the MHC affects individual fitness, population dynamics and viability. We focus on three main areas: the types of information that have been used to detect the action of selection on MHC genes; the relative contributions of parasite-mediated and sexual selection on the maintenance of MHC diversity; and possible future lines of research that may help resolve some of the unanswered issues associated with MHC evolution.

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The evolutionary ecology of the major histocompatibility complex.

We have determined the sequence of a 4-Mb interval on rat chromosome 20p12 that encompasses the rat major histocompatibility complex (MHC). This is the first report of a finished sequence for a segment of the rat genome and constitutes one of the largest contiguous sequences thus far for rodent genomes in general. The rat MHC is, next to the human MHC, the second mammalian MHC sequenced to completion. Our analysis has resulted in the identification of at least 220 genes located within the sequenced interval. Although gene content and order are well conserved in the class II and class III gene intervals as well as the framework gene regions, profound rat-specific features were encountered within the class I gene regions, in comparison to human and mouse. Class I region-associated differences were found both at the structural level, the number, and organization of class I genes and gene families, and, in a more global context, in the way that evolution worked to shape the present-day rat MHC.

/pdf/the-genomic-sequence-and-comparative-analysis-of-the-rat-2phairg5zn.pdf

The genomic sequence and comparative analysis of the rat major histocompatibility complex.

Mercuric chloride induces anti-glomerular basement membrane antibodies in the Brown-Norway rat. Various other inbred rat strains (Lewis, Wistar AG, August, PVG/c) were not found t o be able to produce such antibodies under the same experimental conditions. Hybrids (F1, F2 and F1 × LEW) were bred from Brown-Noway and Lewis rats and injected with mercuric chloride. It has been demonstrated that the induction of anti-glomerular basement membrane antibodies by mercuric chloride in these crosses is under genetic control. The response was found t o depend on two or three genes one of which was H-1-linked. The negative results obtained with L.BN congenic rats were in complete agreement with this conclusion.

Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat: genetic control.

This review of the RT1 complex, the major histocompatibility complex (MHC) of the rat, focuses on genetic, genomic, evolutionary, and functional aspects at the molecular level. The class I, class II, and framework genes are listed. The physical map of the RT1 complex as revealed by analysis of clonal contigs is compared with the human and mouse MHC, and the degree of orthologous relationship is outlined. Elucidation of the RT1 complex provides important information for using the rat as a model of experimental transplantation and complex diseases.

The major histocompatibility complex of the rat (Rattus norvegicus)

The antibody response of different inbred chicken lines to the synthetic polypeptide (T, G)-A–L is described It is shown by analysis of backcross hybrids that a major gene controlling this response is linked to the major histocompatibility system of chicken This result is discussed with respect to its relation to the structure of major histocompatibility systems of mammals

Evidence for an association between immune responsiveness of chicken to (T, G)-A--L and the major histocompatibility system.

The organization of the three major histocompatibility complex (Mhc)-linked heat shock protein 70 (Hsp70) genesHsp70-1, Hsp70-2, andHsp70-3, and the nucleotide sequences of these genes, are presented for the rat.Hsp70-1 andHsp70-2 gene products are identical at the amino acid level. From the pattern of sequence similarity of the orthologous Mhc-linkedHsp70 genes of rat, human, and mouse, it is concluded that the gene duplications leading to the three-gene cluster occurred before the separation of the primate and rodent lines and that theHsp70-1 andHsp70-2 genes of rat and human might have undergone homogenization of their sequences.

Eberhard Günther

Papers

The genomic sequence and comparative analysis of the rat major histocompatibility complex.

Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat: genetic control.

The major histocompatibility complex of the rat (Rattus norvegicus)

Evidence for an association between immune responsiveness of chicken to (T, G)-A--L and the major histocompatibility system.

Comparative analysis of the three major histocompatibility complex-linked heat shock protein 70 (Hsp70) genes of the rat.