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MHC and Scent

MHC and Scent. MHC. MHC molecules play an important role in the immune system and autoimmunity. A MHC molecule inside the cell takes a fragment of those proteins and displays it on the cell surface. The protein fragment is sometimes compared to a hot dog, and the MHC protein to the bun.

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MHC and Scent

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  1. MHC and Scent

  2. MHC • MHC molecules play an important role in the immune system and autoimmunity. • A MHC molecule inside the cell takes a fragment of those proteins and displays it on the cell surface. • The protein fragment is sometimes compared to a hot dog, and the MHC protein to the bun. • When the MHC-protein complex is displayed on the surface of the cell, it can be presented to a nearby immune cell, usually a T cell.

  3. MHC • Because MHC genes must defend against a great diversity of microbes in the environment, the MHC genes themselves must be diverse • MHC genes vary greatly from individual to individual, that is, MHC alleles have polymorphism (diversity).

  4. MHC • There are three general classes of MHC molecules: Class I, Class II and Class III. • Class I MHC molecules are found on almost all cells and present proteins to cytotoxic T cells. • Class II MHC molecules are found on certain immune cells themselves, chiefly macrophages and B cells, also known as antigen-presenting cells • Class III has a function very different from that of class I and class II, it has a locus between the other two (on chromosome 6 in humans)

  5. MHC • In humans, there are 3.6-Mb (3,600,000 base pairs) on the MHC region on chromosome 6 • The best-known genes in the MHC region are the subset that encodes antigen-presenting proteins on the cell surface. • In humans, these genes are referred to as human leukocyte antigen (HLA) gene

  6. MHC • The major histocompatibility complex is encoded by several genes located on human chromosome 6. • Class I molecules are encoded by the BCA region • Class II molecules are encoded by the D region. • A region between these two on chromosome 6 encodes class III molecules, including some complement components.

  7. MHC

  8. Human Leukocyte Antigen • The most intensely studied HLA genes are the nine so-called classical MHC genes: HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1. • In humans, the MHC is divided into three regions: Class I, II, and III. • The A, B, C, E, F, and G genes belong to MHC class I, whereas the six D genes belong to class II.

  9. MHC • MHC genes are expressed in codominant fashion. • This means that the alleles (variants) inherited from both parents are expressed equally

  10. Class I • Class I molecules are composed of two polypeptide chains; one encoded by the BCA region and another (ß2-microglobulin) that is encoded on chromosome 15. • The MHC-encoded polypeptide is about 350 amino acids long and glycosylated, giving a total molecular weight of about 45 kDa. • This polypeptide folds into three separate domains called alpha-1, alpha-2 and alpha-3.

  11. MHC Class I

  12. Class I • ß2-microglobulin is a 12 kDa polypeptide that is non-covalently associated with the alpha-3 domain. • Between the alpha-1 and alpha-2 domains lies a region bounded by a beta-pleated sheet on the bottom and two alpha helices on the sides. • This region is capable of binding (via non-covalent interactions) a small peptide of about 10 amino acids.

  13. Class I and Class II

  14. Class I • There are 3 Class-I genes, named in humans HLA-A, HLA-B and HLA-C • Each person inherits a set of genes from each parent • Any cell in an individual can express 6 different types of MHC-I molecules • These molecules are present in the surface of all nucleated cells and platelets

  15. Class II • In the Class-II locus, each person inherits a couple of genes HLA-DP (DPA1 and DPA2, which encode α and β chains • HLA-DQ (DQA1 and DQA2, for α and β chains) • One gene HLA-DRα (DRA1) and • One or two genes HLA-DRβ (DRB1 and DRB3, -4 or -5). • That means that one heterozygous individual can inherit 6 or 8 class II alleles, three or four from each parent.

  16. MHC Class II

  17. MHC Class II • MHC-II molecules in humansOnly found on Dendritic cells, mononuclear phagocytes, B lymphocytes, some endothelial cells, epithelium of thymus

  18. Haplotypes • The set of alleles which is present in each chromosome is called MHC haplotype. • In humans, each HLA allele is named with a number. • For instance, for a given individual, his haplotype might be HLA-A2, HLA-B5, HLA-DR3, etc... • Each heterozygous individual will have two MHC haplotypes, one in each chromosome (one of paternal origin and the other of maternal origin).

  19. The MHC genes are highly polymorphic • The polymorphism is so high that in a mixed population there are not two individuals with exactly the same set of MHC genes and molecules,with the exception of identical twins.

  20. Polymorphism • The polymorphic regions in each allele are located in the region for peptide contact, which is going to be displayed to the lymphocyte • For this reason, the contact region for each allele of MHC molecule is highly variable, as the polymorphic residues of the MHC will create specific clefts in which only certain types of residues of the peptide can enter

  21. MHC • In MHC polymorphism is very high • It is estimated that in the population there are at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR and 90 alleles for DQ. • HLA-C and HLA-DP molecules show low polymorphism

  22. MHC • It has been suggested that MHC plays a role in the selection of potential mates, via olfaction.

  23. MHC • MHC genes make molecules that enable the immune system to recognize invaders; in general, the more diverse the MHC genes of the parents the stronger the immune system of the offspring. • It would be beneficial, therefore, to have evolved systems of recognizing individuals with different MHC genes and preferentially selecting them to breed with.

  24. MHC • Yamazaki et al. (1976) showed this to be the case for male mice, which show a preference for females of different MHC

  25. MHC • In 1995, Swiss biologist Claus Wedekind determined MHC-dissimilar mate selection tendencies in humans • A group of female college students smelled t-shirts that had been worn by male students for two nights, without deodorant, cologne, or scented soaps. An overwhelming number of women preferred the odors of men with dissimilar MHCs to their own.

  26. MHC • In women, paternally inherited HLA-associated odors influence odor preference and may serve as social cues. • MHC is related to mating choice in some human populations. • Rates of early pregnancy loss are lower in couples with dissimilar MHC genes

  27. MHC odours are not required or sufficient for recognition of individual scent owner • This paper proposes an associative model of scent owner recognition in which volatile scent profiles, contributed by both fixed genetic and varying non-genetic factors, are learnt in association with a stable non-volatile ownership signal provided by other highly polymorphic urine components.

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