Difference Between Major and Minor Histocompatibility Antigens

The key difference between major and minor histocompatibility antigens is that major histocompatibility antigens are glycoproteins coded by human leukocyte antigen (HLA) genes while minor histocompatibility antigens are small peptides coded by either autosomal chromosomes or by Y-chromosome.

There are groups of complex histocompatibility antigens. They are major histocompatibility antigens (MHC) and minor histocompatibility antigens (MiHA). MHCs are HLA molecules, while MiHAs are non-HLA molecules. MHC causes rapid and strong immunoreaction to graft, while MiHA causes slow and weak immunoreaction to the graft. There are two classes of MHC as MHC I and MHC II. They are present in almost all nucleated cells in the human body.

CONTENTS

1. Overview and Key Difference
2. What are Major Histocompatibility Antigens
3. What are Minor Histocompatibility Antigens
4. Similarities Between Major and Minor Histocompatibility Antigens
5. Side by Side Comparison – Major vs Minor Histocompatibility Antigens in Tabular Form
6. Summary

What are Major Histocompatibility Antigens?

On the surface of healthy cells, there are special molecules called major histocompatibility complex. 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, etc., 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.

What are Minor Histocompatibility Antigens?

Minor histocompatibility antigens (MiHA) 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 acids 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.

What are the Similarities Between Major and Minor Histocompatibility Antigens?

• Minor histocompatibility antigens are bound to MHC I and MHC II antigens.
• Both are present on the surface of the cells.
• They are proteins.
• In fact, they are cell surface receptors.
• They are alloantigens.
• Immune responses are mediated by T cells for both types.

What is the Difference 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 MiHA are Human Leukocyte Antigen (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 human leukocyte antigen (HLA) genes while MiHAs are encoded by either autosomal chromosomes or by Y-chromosome.

Below infographic shows more differences between major and minor histocompatibility antigens.

Summary – Major vs Minor Histocompatibility Antigens

Major histocompatibility antigens play a critical role in adaptive immunity. They present foreign antigens to T cells. T cells detect them and activate the immune responses against them. Minor histocompatibility antigens are small peptides that are found on the cell surfaces bound to MHC I and MHC II. MHCs are glycoproteins while MiHAs are small peptides. Thus, this summarizes the difference between major and minor histocompatibility antigens.

Reference:

1. Janeway, Charles A, and Jr. “The Major Histocompatibility Complex and Its Functions.” Immunobiology: The Immune System in Health and Disease. 5th Edition., U.S. National Library of Medicine, 1 Jan. 1970, Available here.
2. Summers, Corinne, et al. “Minor Histocompatibility Antigen-Specific T Cells.” Frontiers in Pediatrics, Frontiers Media S.A., 3 June 2020, Available here.

Image Courtesy:

1. “MHC expression” By derivative work: Zionlion77 (talk)MHC_Class_1.svg: User atropos235 on en.wikipediaMHC_Class_2.svg: User atropos235 on en.wikipedia – MHC_Class_1.svgMHC_Class_2.svg (CC BY-SA 3.0) via Commons Wikimedia

2. “GVHD initiation” (CC BY 4.0) via Commons Wikimedia