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Scents play a central role in rodent societies, communicating information about identity (species, sex, individual, kinship) and status (social, reproductive, health, age). This requires the interaction between volatile and involatile molecular components of scents, the spatial deposition pattern of scent marks, and time of deposition. The major histocompatibility complex (MHC) and major urinary proteins (MUPs) are both highly polymorphic systems that contribute to scents. Most studies have focused on MHC in inbred laboratory rodents. However, studies of wild rodents are revealing that MUPs provide a species and sex-specific genetic identity signature that also underlies individual and kin recognition in house mice. MUPs are mediators of both identity and current status information. Although MHC contributes to the recognition of familiar scents, there is little evidence that it provides direct information about genetic identity.

The Major Histocompatibility Complex on chromosome 6 encodes a diverse array of genes involved in the immune and inflammatory response. The region is remarkably polymorphic and has been associated with susceptibility to autoimmune and infectious disease. The approaches to defining and understanding the nature and consequences of genetic diversity in the MHC are reviewed in terms of the biology of encoded molecules, evolutionary selective pressures and relationship to disease. Progress in haplotypic analysis of the MHC, resequencing and fine mapping are discussed together with insights from structural biology and detailed functional characterisation of the consequences of genetic diversity. The role of genetic variation in the MHC for a number of specific diseases are reviewed including rheumatoid arthritis, haemochromatosis, type 1 diabetes, coeliac disease, narcolepsy and sarcoidosis with emphasis on progress in defining the functional basis of disease associations, for example modulation of alternative splicing by genetic variation associated with sarcoidosis.

This chapter focuses on genes under selection. Much of what is known about ‘ecologically relevant’ genetic variation at the level of DNA sequences comes from studies of genes of the major histocompatibility complex (Mhc genes). This gene family codes for cell-surface proteins involved in immunoresistance in vertebrates. The chapter briefly reviews evidence for selection on Mhc loci, links to parasite resistance, and consequences of lost genetic variation at Mhc loci. It also considers other candidate genes. Examples of such that may be relevant in conservation are genes coding for animal pigmentation (such as mc1r) and clock genes (involved in photoperiodism). It is shown that selection may both maintain genetic variation, through balancing selection, and erode it, through purifying and directional selection.

This chapter discusses antigen processing, presentation, and T cell interaction. The central nervous system (CNS) is protected by a blood-brain barrier (BBB) designed to minimize the passage of immune cells and macromolecules into the brain parenchyma. In the normal CNS parenchyma antigen-presenting cells (APCs) are functionally inactivated and lack expression of major histocompatibility complex (MHC) molecules. Nevertheless, the CNS is routinely surveyed by activated T lymphocytes. Perivascular macrophages situated adjacent to the endothelium cells of the blood vessels take up and present antigens to T lymphocytes. Most cells of the brain parenchyma are immunologically quiescent in the healthy CNS, but can be stimulated to become facultative APCs that process and present antigens via their MHC molecules to T lymphocytes in neuroinflammatory diseases.

This chapter aims at clarifying the notions of self and nonself through a historical analysis. I show that the relationship between immunity and the identity of the organism, as well as the idea that an immune response is due to the penetration in the organism of foreign bodies, both preexist Burnet’s self-nonself framework. The crucial step accomplished by Burnet is that he transformed these apparently self-evident observations in a scientific problem, asking how the organism learns to not attack its own constituents. Explaining the tolerance to the self is thus the starting point of the self-nonself theory. Thanks to a detailed analysis of Burnet’s scientific writings, I demonstrate the link between the self-nonself framework and Burnet’s famous clonal selection theory. I make clear how the very conception of the self changed significantly throughout Burnet’s scientific reflection. Finally, I show that the self-nonself theory is still dominant in today’s immunology.