Cellular Distribution of MHC Molecules

In general, the classical class I MHC molecules are expressed on most nucleated cells, but the level of expression differs among different cell types. The highest levels of class I molecules are expressed by lymphocytes, where they constitute approximately 1% of the total plasma-membrane proteins, or some 5 X 105 molecules per cell. In contrast, fibroblasts, muscle cells, liver hepatocytes, and neural cells express very low levels of class I MHC molecules. The low level on liver cells may contribute to the considerable success of liver transplants by reducing the likelihood of graft recognition by Tc of the recipient. A few cell types (e.g., neurons and sperm cells at certain stages of differentiation) appear to lack class I MHC molecules altogether.

As noted earlier, any particular MHC molecule can bind many different peptides. Since the MHC alleles are codomi-nantly expressed, a heterozygous individual expresses on its cells the gene products encoded by both alleles at each MHC locus. An F1 mouse, for example, expresses the K, D, and L from each parent (six different class I MHC molecules) on each of its nucleated cells (Figure 7-16). A similar situation occurs in humans; that is, a heterozygous individual expresses the A, B, and C alleles from each parent (six different class I MHC molecules) on the membrane of each nucleated cell. The expression of so many class I MHC molecules allows each cell to display a large number of peptides in the peptide-binding clefts of its MHC molecules.

In normal, healthy cells, the class I molecules will display self-peptides resulting from normal turnover of self proteins. In cells infected by a virus, viral peptides, as well as self-peptides, will be displayed. A single virus-infected cell should be envisioned as having various class I molecules on its membrane, each displaying different sets of viral pep-tides. Because of individual allelic differences in the peptide-binding clefts of the class I MHC molecules, different individuals within a species will have the ability to bind different sets of viral peptides.

Unlike class I MHC molecules, class II molecules are expressed constitutively only by antigen-presenting cells, pri-

Dk Dd

Class I molecules

Kk V

Maternal MHC

Maternal MHC

Kk

IAakßk

IEakßk

Dk

Lk

Kd IAadßd

IEadßd

Dd

Ld

Mhc Diagram Paternal And Maternal

Class II IE a d ß molecules

Paternal MHC

Paternal MHC

Class II IE a d ß molecules

FIGURE 7-16

Diagram illustrating various MHC molecules expressed on antigen-presenting cells of a heterozygous H-2k/d mouse. Both the maternal and paternal MHC genes are expressed. Because the class II molecules are heterodimers, heterologous molecules containing one maternal-derived and one paternal-derived chain are produced. The ^-microglobulin component of class I molecules (pink) is encoded by a gene on a separate chromosome and may be derived from either parent.

marily macrophages, dendritic cells, and B cells; thymic epithelial cells and some other cell types can be induced to express class II molecules and to function as antigen-presenting cells under certain conditions and under stimulation of some cytokines (see Chapter 8). Among the various cell types that express class II MHC molecules, marked differences in expression have been observed. In some cases, class II expression depends on the cell's differentiation stage. For example, class II molecules cannot be detected on pre-B cells but are expressed constitutively on the membrane of mature B cells. Similarly, monocytes and macrophages express only low levels of class II molecules until they are activated by interaction with an antigen, after which the level of expression increases significantly.

Because each of the classical class II MHC molecules is composed of two different polypeptide chains, which are encoded by different loci, a heterozygous individual expresses not only the parental class II molecules but also molecules containing a and p chains from different chromosomes. For example, an H-2^ mouse expresses IA^ and IE^ class II molecules; similarly, an H-2d mouse expresses IAd and IEd molecules. The F1 progeny resulting from crosses of mice with these two haplotypes express four parental class II molecules and four molecules containing one parent's a chain and the other parent's p chain (as shown in Figure 7-16). Since the human MHC contains three classical class II genes (DP, DQ, and DR), a heterozygous individual expresses six parental class II molecules and six molecules containing a and p chain combinations from either parent. The number of different class II molecules expressed by an individual is increased further by the presence of multiple p-chain genes in mice and humans, and in humans by multiple a-chain genes. The diversity generated by these mechanisms presumably increases the number of different antigenic peptides that can be presented and thus is advantageous to the organism.

Was this article helpful?

+1 0
Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook


Responses

  • ARMI
    What is cellular distribution of mhc molecules?
    4 years ago
  • jeremy
    How many MHC molecules are in each cell?
    11 months ago
  • SILKE
    How many MHC molecules on the surface of a normal cell?
    6 months ago
  • ralf
    How many MHC II molecue single cell?
    5 months ago
  • ernesta
    How many differnt MHCII on a cell?
    3 months ago

Post a comment