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Major Histocompatibility Complex and Autoimmune Disease
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Ursula Holzer, Gerald T. Nepom
The major histocompatibility complex (MHC) encodes a large number of molecules which are key participants in the function of the immune system. Included in the human MHC, known as human leukocyte antigen (HLA), are two classes of HLA molecules which are highly polymorphic, and which provide genetic restriction for T lymphocyte responses: HLA class I and HLA class II. Several of the HLA class II molecules are highly associated with, and likely to have a major role in, susceptibility to autoimmune diseases. However, the molecular mechanisms involved are still unclear. In this chapter we address the structure of the HLA molecules and the mechanisms for presenting antigens to the immune system, as well as the correlation of specific HLA alleles with autoimmune diseases.
Human Odor: An Overview of Current Knowledge and Experimental Designs
Published in G. Thilagavathi, R. Rathinamoorthy, Odour in Textiles, 2022
The major histocompatibility complex (MHC) is the most diverse part of the genome; in humans this genetic coding region is referred to as the human leukocyte antigen (HLA). MHC molecules have two categories, Class I and Class II. Class I molecules are present in all nucleated cells within the body, and their purpose is the processing and recognition by T-cells of any foreign antigen. Class II MHC molecules are present on certain lymphocytes, and their purpose is to present antigens for recognition with other cells to increase immune response (Eggert et al. 1999). Thus, the HLA locus effectively represents an immunological “identity” of an individual. Seminal work in this area has been conducted with mice animal models exhibiting odor preference of conspecifics, which differed in MHC genes (Yamazaki et al. 1976). This foundational work caused an eruption of research in this area, investigating the MHC complex as a source of an individual “odortype” (Havlicek and Roberts 2009; Kwak et al. 2010). Of special interest in the research community is the evaluation of MHC function with respect to mate selection or kin recognition (Yamazaki and Beauchamp 2007). The hypothetical mechanism proposed is that due to immunological individuality defined by the MHC, the allele expression creates a specific individual odor signature, in both biological body fluids and general body odor (Yamazaki et al. 1978). A recent study performed a comprehensive meta-analysis to investigate available evidence and study design approaches with respect to mate selection and MHC dissimilarity. Recommendations were the need of larger sampling sizes, geographical sites, and even cultural diversity in order to fully understand this complex interaction between a “genetic” odortype and mating preferences (Havlíček, Winternitz, and Roberts 2020). All these studies are based on the premise that there is a specific odor compound along with a corresponding combination of MHC genes. The question yet to be answered, however, is the exact mechanism that leads the MHC complex to express a particular odor “fingerprint”.
Head Transplantation: The Immune System, Phantom Sensations, and the Integrated Mind
Published in The New Bioethics, 2018
In the vocabulary of immunology, the expressions ‘self’ and ‘non-self’ may be thrown about with such abandon that these expressions are easily used to conflate issues in the broader language of personhood. It is important, therefore, to remember that when these expressions are used in immunology they are concerned with molecular recognition. The immune system consists of a network of molecular and cellular systems that undertake the critical function of differentiating that which is described in immunological terms as ‘self’ from that which is ‘non-self’ and imposes a level of identity on cells and tissues that must be considered in any transplant operation. These systems are typically grouped under the general headings ‘innate immunity’ and ‘adaptive immunity’ and involve more than 1600 genes (Abbas et al. 2005). Underpinning the adaptive responses are protein complexes brought together under the general heading the ‘major histocompatibility complex’ (MHC), also referred to as ‘human leukocyte antigens’ (HLA) when specific human MHC proteins are being referenced. MHC antigens are grouped into a number of classes, which, in broad terms, might be said to share function, insofar as they may, for example, process proteins into small chunks that are then presented to the T-cell receptor (TcR) on T-cells (La Gruta et al. 2018). They do, however, differ structurally from each other and serve different specific tasks. One of these, MHC class I (MHC-I, of which HLA-A, HLA-B, and HLA-C are members), is normally present on all nucleated cells, and subclasses of this are expressed within the first three days of the life of a human embryo (Wang et al. 2009). The absence MHC-I expression on cells leaves them vulnerable to destruction through the action of the MHC-I-sensing ‘killer cell immunoglobulin-like receptor’ (KIR), present on subpopulations of immune cells known as Natural Killer (NK) cells and subsets of T-cells. An important exception to this is the red blood cell population. Red cells do not express MHC-I, instead escaping destruction by NK cells through the expression of another protein, CD47 (Wang et al. 2010). Alongside the MHC-I, the expression of MHC class II (MHC-II, comprising HLA-DP HLA-DQ and HLA-DR in humans) and minor histocompatibility antigens (MiHA) like the male-specific H-Y antigen. The result of this is that, by the 8-cell stage of the embryo, the embryo is immunologically reactive with respect to the mother and its continued development requires the induction of immunological tolerance within the womb to prevent fetal rejection and miscarriage (Fernandez et al. 1999; Larsen et al. 2013; Colucci 2017).