Difference Between MHC Class 1 and 2

Main Difference – MHC Class 1 vs 2

Major Histocompatibility Complex (MHC) is a tightly-linked, gene clusters found in mammals. MHC in humans is known as HLA (human leukocyte antigen) complex and in mice, MHC is known as H-2 complex. HLA complex is the most polymorphic region of the human genome. MHC genes are expressed to produce surface antigens on the cell membrane. The main function of MHC is to aid in the development of humoral and cell-mediated immune responses by presenting antigens to T cells. The three classes of MHC molecules can be identified as class 1, 2, and 3. The main difference between MHC class 1 and 2 is that MHC class 1 molecules present antigens to cytotoxic T cells with CD8+ receptors whereas MHC class 2 molecules present antigens to helper T cells with CD4+ receptors.

Key Areas Covered

1. What is MHC Class 1
– Definition, Structure, Antigen Presentation
2. What is MHC Class 2
– Definition, Structure, Antigen Presentation
3. What are the Similarities Between MHC class 1 and 2
– Outline of Common Features
4. What is the Difference Between MHC class 1 and 2
– Comparison of Key Differences

Key Terms: Antigen Presenting Cells, Cytotoxic T Cells, Endogenous Antigens, Exogenous Antigens, HLA, Helper T Cells, MHC (major histocompatibility complex)

What is MHC Class 1

MHC class 1 refers to one class of major histocompatibility complex molecules found on the surface of all nucleated cells in mammals. MHC class 1 molecule is composed of three alpha domains (alpha 1, alpha 2, and alpha 3) and a single beta domain. Alpha domains are encoded by the chromosome 6 while the beta domain is encoded by chromosome 11. The alpha 3 domain serves as the membrane-spanning domain. The alpha 1 and alpha 2 domains consist of most variable amino acid sequences and antigens are bound to these two domains. The structure of the MHC class 1 molecule is shown in figure 1.

Figure 1: MHC Class 1

MHC class 1 molecules are expressed on almost every nucleated cell in the body. Hence, they present endogenous antigens that originate from the cytoplasm. However, these endogenous antigens can be either self-proteins or foreign protein such as viral proteins produced within the cell. Generally, viral proteins are produced inside animal cells with the help of cellular machinery of the host. Upon presentation on the cell membrane, antigens are recognized by cytotoxic T cells. MHC class 1 molecules are involved in the presentation of antigens that belong to every type of protein produced inside the cell. These antigens are monitored by killer T cells. This identification serves as a part of the surveillance system that destroys over-abundant or unfamiliar antigen presenting cells. Thus, malignant cells, as well as virus-harboring cells, can be destroyed.

What is MHC Class 2

MHC class 2 refers to a class of major histocompatibility complex molecules mainly found on antigen presenting cells such as macrophages, dendritic cells, and B cells. MHC class 2 molecule is composed of two alpha (alpha 1 and alpha 2) and two beta (beta 1 and beta 2) domains. Both alpha and beta domains of the MHC class 1 molecules are encoded by chromosome 6. The alpha 2 and beta 2 domains serve as the membrane-spanning domains while alpha 1 and beta 1 domains serve as antigen-presenting domains. The structure of the MHC class 2 molecule is shown in figure 2.

Figure 2: MHC Class 2

MHC class 2 molecules are expressed on specialized antigen-presenting immune cells, including macrophages, dendritic cells, and B cells. Macrophages are the most professional phagocytes that engulf bacteria and virus-like foreign particles. Dendritic cells are also a type of phagocytes that present antigens to T cells. B cells produce antibodies during humoral immunity. MHC class 2 molecules present exogenous antigens. The exogenous antigens are originated extracellularly from bacteria-like foreign particles. The phagocyted pathogens are degraded inside the antigen presenting cells and peptide fragments are presented on the cell membrane with the help of MHC class 2 molecules. These antigens are recognized by helper T cells, activating them. The activated helper T cells release lymphokines, attracting other cells that destroy the antigenic material.

Similarities Between MHC Class 1 and 2

MHC class 1 and 2 are two types of MHC molecules that are encoded by gene clusters of MHC.
Both MHC class 1 and 2 are surface antigens that are expressed on the cell membrane.
Both MHC class 1 and 2 present antigens to T cells.
Both MHC class 1 and 2 molecules are involved in the development of immune responses against foreign antigens.
Both MHC class 1 and 2 are responsible for the graft rejection during various organ and tissue transplantation.

Definition

MHC Class 1: MHC class 1 are a class of major histocompatibility complex molecules found on the surface of all nucleated cells in mammals.

MHC Class 2: MHC class 2 are a class of major histocompatibility complex molecules mainly found on antigen presenting cells such as macrophages, dendritic cells, and B cells.

Occurrence

MHC Class 1: MHC class 1 molecules are expressed on all types of nucleated cells in the body.

MHC Class 2: MHC class 2 molecules are expressed on the antigen presenting cells such as B cells, macrophages, and dendritic cells.

Structure

MHC Class 1: MHC class 1 molecules are composed of three alpha domains and a single beta domain.

MHC Class 2: MHC class 2 molecules are composed of two alpha and beta domains.

Membrane-spanning Domain

MHC Class 1: MHC class 1 molecules are composed of a single, membrane-spanning, alpha domain.

MHC Class 2: MHC class 2 molecules are composed of two membrane-spanning alpha and beta domains.

Encoded Genes

MHC Class 1: The three main types of MHC class 1 genes are MHC-A, MHC-B, and MHC-C.

MHC Class 2: The main type of MHC class 2 gene is MHC-D.

Encoded Chromosomes

MHC Class 1: The alpha domains are encoded on the MHC locus of chromosome 6 and beta chains are encoded on chromosome 15.

MHC Class 2: MHC class 2 genes are encoded on the chromosome 6.

Nature of Antigen Presenting

MHC Class 1: MHC class 1 molecules present endogenous antigens originated from the cytoplasm.

MHC Class 2: MHC class 2 molecules present exogenous antigens originated extracellularly from foreign bodies such as pathogens.

Antigen-presenting Domains

MHC Class 1: The alpha 1 and alpha 2 domains are involved in the presentation of antigens in MHC class 1 molecules.

MHC Class 2: The alpha 1 and beta 2 domains are involved in the antigen presentation in MHC class 2 molecules.

Responsive Cells

MHC Class 1: MHC class 1 present antigens to cytotoxic T cells.

MHC Class 2: MHC class 2 present antigens to helper T cells.

Responsive Co-receptor

MHC Class 1: MHC class 1 molecules bind to the CD8+ receptors on the cytotoxic T cells.

MHC Class 2: MHC class 2 molecules bind to the CD4+ receptors on the helper T cells.

Role

MHC Class 1: MCH class 1 is responsible for the clearance of endogenous antigens.

MHC Class 2: MHC class 2 is responsible for the clearance of exogenous antigens.

Conclusion

MHC class 1 and 2 are two types of surface antigens involved in the development of adaptive immune responses against non-self. MHC class 1 molecules present endogenous antigens to cytotoxic T cells. MHC class 2 molecules present exogenous antigens to helper T cells. Thus, the main difference between MHC class 1 and 2 molecules is the type of antigens presented by each type of MHC molecules.

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.

Image Courtesy:

1. “MHC Class 1” By User atropos235 on en.wikipedia – Own work (CC BY 2.5) via Commons Wikimedia
2. “MHC Class 2” By User atropos235 on en.wikipedia – Own work (CC BY 2.5) via Commons Wikimedia