Major Histocompatibility Complex development

Lymphocytes, the effector cells of the acquired immune system, include morphologically indistinguishable T and B cells, the former divided into CD4+ T helper cells and CD8+ cytotoxic T cells. Since the functions of those cell subsets differ so drastically, it became important to develop tools to distinguish them from each other. Efforts to identify cell subsets according to their expression of different surface antigens have been successful, including various Cluster of Determination (CD) markers (Table 23.1). In addition, cross-reactive monoclonal antibodies, and subsequently developed species-specific polyclonal and monoclonal antibodies towards the major histocompatibility complex (MHC) have been used to label cells in circulation and in tissue sections (Table 23.1). 

This provides potential defensive proteins directed at almost every imaginable invader. It also ensures that every individual has a set of proteins that labels its own cells as "self," and that virtually every individual on earth has cell surface proteins different from those of every other person. In both the innate and adaptive responses the immune system must carefully distinguish "self" from "nonself."36 37 In the innate system this discrimination developed during evolution of the host and its pathogens. In the adaptive system it depends upon interaction of the T cells with surface molecules, primarily those of the major histocompatibility complex (MHC). 

Development of Novel Major Histocompatibility Complex Class I and Class 11-Deficient NOD-SCIDIL2R Gamma Chain Knockout Mice for Modeling Human Xenogeneic Graft-Versus-Host Disease... 

Rothenberg, B. E. and Voland, J. R. (1996). Beta2 knockout mice develop parenchymal iron overload a putative role for class I genes of the major histocompatibility complex in iron metabolism. Proc. Natl. Acad. Sci. USA 93 1529-1534. 

Di Lorenzo, T. P., Graser, R. T., Ono, T., Christianson, G. J., Chapman, H. D., Roopenian, D. C., Nathenson, S. G. and Serreze, D. V. (1998). Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor alpha chain gene rearrangement. Proc. Natl. Acad. Sci. USA 95, 12538-12543. 

Katz, J., Benoist, C. and Mathis, D. (1993). Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice. Eur. J. Immunol. 23, 3358-3360. 

The requirement of multifunctional peptide complexes is perhaps most obvious for the development of subunit peptide vaccines. Successful immunizations with peptide antigens cannot be achieved without the inclusion of a bystander T-helper cell determinant in the chemical entity (4) or in the immunizing cocktail (5). For outbred animals and humans, multiple peptide epitopes, representing determinants of more than one major histocompatibility complex (MHC) proteins, are used to overcome subunit vaccine unresponsiveness, and this also improves antigen presentation in inbred animals (6). 

The cause of type 1 diabetes is not fuUy understood. An autoimmune attack (to the /3-cells of the pancreas) may be triggered by reaction to an infection, for example by one of the viruses of the Coxsackie virus family or German measles, although the evidence is inconclusive. Individuals may display genetic vulnerability an observed inherited tendency to develop type 1 diabetes has been traced to particular human leukocyte antigen (HLA) genotypes (the major histocompatibility complex (MHC) in humans is known as the HLA system). Environmental factors can also strongly influence expression of type 1 diabetes. 

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