Autoimmunity Can Be Associated with the MHC or with Particular TCell Receptors

Several types of studies have supported an association between expression of a particular MHC allele and susceptibility to autoimmunity, an issue covered in detail in Chapter 7. The strongest association between an HLA allele and an autoimmune disease is seen in ankylosing spondylitis, an inflammatory disease of vertebral joints. Individuals who have HLA-B27 have a 90 times greater likelihood of developing ankylosing spondylitis than individuals with a different HLA-B allele. However, the existence of such an association should not be interpreted to imply that the expression of a particular MHC allele has caused the disease, because the relationship between MHC alleles and development of autoimmune disease is complex. It is interesting to note that, unlike many other autoimmune diseases, 90% of the cases of ankylosing spondylitis are male.

The presence of T-cell receptors containing particular Va and Vp domains also has been linked to a number of autoimmune diseases, including experimental EAE and its human counterpart, multiple sclerosis. In one approach, T cells specific for various encephalitogenic peptides of MBP were cloned and their T-cell receptors analyzed. For example, T-cell clones were obtained from PL/J mice by culturing their T cells with the acetylated amino-terminal nonapeptide of MBP presented in association with a class II IAu MHC molecule. Analysis of the T-cell receptors on these clones revealed a restricted repertoire of Va and Vp domains: 100% of the T-cell clones expressed Va 4.3, and 80% of the T-cell clones expressed Vp 8.2. In human autoimmune diseases, evidence for restricted TCR expression has been obtained for both multiple sclerosis and myasthenia gravis. The preferential expression of TCR variable-region genes in these autoimmune T-cell clones suggests that a single epitope might induce the clonal expansion of a small number of pathogenic T cells.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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