An Introduction to Major and Minor Histocompatibility Antigens

On the surface of healthy cells, there are special molecules called major histocompatibility complex (MHC). They play a key role in presenting foreign antigens to immune cells, especially by activating T cells. They work for the adaptive immune system. Major histocompatibility molecules are present in almost all nucleated healthy cells of humans. Mature red blood cells are the only type of human cells that do not have MHC molecules on the surface. Human leukocyte antigen (HLA) genes are the genes that code MHC molecules. Structurally, major histocompatibility antigens are transmembrane glycoproteins having portions that span the plasma membrane.

Generally, MHC molecules vary among individuals. There are two classes of MHC. They are class I MHC antigens and class II MHC antigens. Class I MHC molecules are found in all cells while class II MHC molecules are found only on the surface of antigen-presenting cells such as monocytes, macrophages, and dendritic cells, which are involved in immune reactions. Antigen presentation with MHC II is essential for the activation of T cells. MHC I antigens are essential for the presentation of normal "self" antigens.

While minor histocompatibility antigens (MiHAs) are small peptides found on cell surfaces. Therefore, MiHAs are short segments of proteins which are diverse. They are polymorphic in a given population. Structurally, they are composed of around 9 to 12 amino acid sequences. Generally, they are found associated with MHC antigens on the cell surface. These antigens can be either expressed ubiquitously in most tissues or expressed restrictively in immune cells. Predominantly, they are expressed on hematopoietic cells.

MiHAs are most found on the cellular surface of donated organs. In some organ transplants, they cause immunological responses. But they cause problems of rejection less frequently than MHC. However, even the donor and recipient are identical with regard to MHC genes; minor histocompatibility antigens can also mediate rejection due to amino acid differences.

"Efforts to prevent graft-versus-host disease could be targeted through this pathway by matching for these MiHA or by preventing antigen recognition. Alternatively, these MiHA could be exploited as targets for a more potent graft-versus-malignancy effect," as introduced by a scientist from Creative Biolabs, a biotech company offering minor histocompatibility antigen display service.

There are similarities between major and minor histocompatibility antigens. For example, MiHAs are bound to MHC I and MHC II antigens, and both are proteins present on the surface of the cells. They are all alloantigens, and immune responses are mediated by T cells for both types.

With so many similarities, differences do exist between major and minor histocompatibility antigens. MHC are glycoproteins that are present on the surface of all cells in order to present foreign antigens to immune cells while MiHAs are HLA-presented peptides derived from normal self-proteins. So, this is the key difference between major and minor histocompatibility antigens. MHC molecules are glycoproteins while MiHAs are small proteins. There are two classes of MHCs: MHC I and MHC II. MiHAs are diverse. Moreover, MHCs are coded by HLA genes while MiHAs are encoded by either autosomal chromosomes or by Y-chromosome.

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