Expression of MHC molecules - Discover Biotech

In this article, I briefly describe the expression of MHC molecules.

Table of Contents

MHC molecule and its expression

The major histocompatibility complex (MHC), consists of a group of genes coding for proteins present on cell surfaces that help the immune system recognize foreign substances. The MHC molecules are encoded by a cluster of closely associated genes, known as the MHC locus. There are three classes of MHC molecules, class-I, class II, and class-III.

The expression of MHC not only aids in fighting infection but plays a vital role in maintaining body homeostasis. Most MHC molecules present more self-peptides than foreign antigens to T cells. A healthy cell displays self-MHC class I and self-peptide. An infected cell displays a foreign peptide in class I MHC to cytotoxic T (T_C) cells. It shows a foreign peptide in class II MHC to T helper (T_H) cell.

In primary lymphoid organs, a cell displays a self-peptide in class I and class II MHC to test the autoreactivity of T cells and to maintain tolerance to self-proteins in secondary lymphoid organs.

Intracellular and extracellular antigens presented by MHC

Intracellular antigens are presented by the class-I MHC and cells of our body present self-peptides in the grooves of the MHC class-I molecules. When the class-I self MHC expresses itself with self-peptides, it’s a signal, that shows that the cell is healthy.

A virus-infected cell and tumor cells are devoid of self-MHC class-I and targeted by the NK cells for destruction. In the cytosol, the presence of foreign proteins causes them to proceed towards the grooves of MHC class-I molecules present on the cell surface.

The presence of foreign peptides in the class-I MHC grooves alerts the CD8⁺ T cells for cell destruction. Thus, the cell becomes a target for lysis carried out by the T_C cells.

The MHC class-I molecules present intracellular antigens, whereas the MHC class-II molecules mainly present extracellular antigens. The cells presenting extracellular antigens in the grooves of MHC class-II molecules are known as antigen-presenting cells. They present antigens to CD4⁺ T_H (T helper) cells.

Nearly all nucleated cells express the MHC class-I molecules throughout body

Almost all nucleated cells of our body express the classical MHC class-I molecules. However, the level of expression varies among cells. The highest level of class-I molecules is expressed by lymphocytes.

The lymphocytes contain the MHC class-I molecules, which are approximately 1% of the total plasma membrane proteins. The cells like muscle cells, fibroblasts, some neural cells, and liver hepatocytes express very less to negligible MHC class-I molecules. Thus, it acts as a succor during liver transplantation as the risk of graft rejection is minimized by the recipient.

Certain cell types, like the sperm cells and subsets of neurons at a specific stage of differentiation, do not express the MHC molecules and non-nucleated cells. The red blood cells in mammals also lack expression of the same. Thus, making it difficult for T_C (cytotoxic T cells) cells to target them.

In a healthy cell, the MHC class-I molecules will display self-peptides (resulting from the normal yield of self-proteins inside the cell) on the surface of the cell. However, a cell infected with a virus will display both viral peptides along with self-peptides on the cell surface.

Thus, a virus-infected cell has different class I molecules on its membrane. Apart from virus-infected cells, altered self-cells like aging cells, cancer cells, or allogenic graft cells can be target cells for cytotoxic T cells. When a cell stops expressing the MHC class-I molecules on its surface, it is killed by natural killer cells. The NK cells mark the cell as unhealthy and kill it.

Antigen-presenting cells express the MHC class-II molecules

Antigen-presenting cells (APCs) are professionals in alerting the immune system against an invader and activating T-cell responses. These cells display peptides linked with the class-II MHC molecules to the CD4⁺ T helper cells.

The APCs possess some specificity due to which they can express the MHC class-II molecules. They also deliver a costimulatory signal to the T cells. The professional antigen-presenting cells differ in the expression of the MHC class-II molecules among themselves. It depends on the differentiation stages of the cell or the level of activation.

An antigen-presenting cell activates itself by interacting with a pathogen. The dendritic cells, macrophages, and B lymphocytes are the three professional antigen-presenting cells that differ from each other in the antigen uptake mechanism.

The Dendritic cells are the most efficient professional antigen-presenting cells as they constantly express high MHC class-II molecules. Thus, they can quickly activate the naïve T helper cells by the inherent costimulatory activity.

The macrophages, after activation, express MHC class-II molecules and costimulatory membrane molecules such as CD80/86. The B cells constitutively express MHC class-II molecules at low levels. The B cells expressing MHC class-II molecules, possess surface receptors specific for antigens, which make them more efficient in capturing and presenting antigens.

An APC comes across a pathogen either through a B cell receptor or through a pattern recognition receptor and cytokine signaling. This induces changes in gene expression and thus increases MHC class-II expression.

Some nonprofessional antigen-presenting cells, such as fibroblasts, glial cells, and β cells of the pancreas, express MHC class-II molecules and costimulatory signals under certain conditions. These cells can play the role of professional antigen-presenting cells for a short period in a particular situation, like in a sustained inflammatory response.

Conclusion

The major histocompatibility complex (MHC), consists of a group of genes coding for proteins present on cell surfaces that help the immune system recognize foreign substances. There are three types, Class-I, class-II, and class-III MHC molecules. Almost all nucleated cells express the class-I MHC molecules throughout the body. Expression of the MHC molecules not only aids in fighting infection but also plays a vital role in maintaining body homeostasis.

The cells of our body present self-peptides in the grooves of MHC class-I molecules. When the class-I self MHC expresses itself with self-peptides, then it is a signal showing that the cell is healthy. The NK cells kill a cell when it stops expressing the MHC class-I molecules on its surface.

The antigen-presenting cells present peptides associated with class-II MHC molecules to the CD4⁺ T helper cells. The dendritic cells are the most efficient professional antigen-presenting cells as they constantly express high MHC class-II molecules.