MHC Classes: Structure and Function

MHC Molecules and T Cell Receptors

• There are two classes of MHC molecules: MHC-class I and MHC-class II, which differ in structure and expression pattern in cells.
• MHC-class I molecules bind to CD8 T cell receptors (cytotoxic T cells), while MHC-class II molecules bind to CD4 T cell receptors (helper T cells).

MHC-class I Molecules

• MHC-class I molecules are designed to enable the body to recognize infected cells and destroy them with the help of cytotoxic CD8 T cells.
• They are present on lymphocytes, neutrophils, basophils, eosinophils, and platelets.
• MHC-class I molecules have a deep groove that can bind antigen epitopes of 8-11 amino acids long.
• They display a part of the antigen peptides (the epitope) on the lymphocyte cell surface after the antigen-presenting cell processes or cleaves the antigen.

T Lymphocytes (T cells)

• T cells are born from hematopoietic stem cells found in the bone marrow.
• Immature T cells migrate from the bone marrow to the thymus gland to mature.
• After maturation, T cells express several receptors, including CD3, CD4, CD8, CD28, and CD45.
• T cells do not recognize a soluble antigen in its free form; an antigen must be presented to the T cell receptor through antigen-presenting cells with the help of MHC molecules.

Antigen-Presenting Cells

• Antigen-presenting cells include macrophages, B cells, dendritic cells, neutrophils, basophils, eosinophils, and platelets.
• They express MHC molecules on their surface.
• The role of antigen-presenting cells is to cleave or process antigens into smaller fragments and present the epitopes on MHC molecules.

CD4 and CD8 T Cell Receptors

• CD4 T cells are called helper T cells and are responsible for activating other immune cells for antigen killing.
• CD4 T cells recognize antigen that is bound to MHC-class II molecules of the antigen-presenting cell.
• CD8 T cells are called cytotoxic T cells and are responsible for direct killing of the antigen through secretion of cytotoxic molecules.
• CD8 T cells recognize antigen that is bound to MHC-class I molecules of the antigen-presenting cell.

Structure of T Cell Receptors

• T cell receptors consist of two chains, α and β, connected by a disulfide bond.
• Each chain has carbohydrate side chains attached to each domain.
• The α and β chains have a short cytoplasmic tail at the carboxyl-terminal end.
• A short stalk segment connects the domains to the transmembrane region.

Functions of CD8 T cells

• CD8 T cells are important for immune defense against intracellular pathogens, including viruses, bacteria, and cancer cells.
• When activated, CD8 T cells have three major mechanisms to kill infected cells: secretion of cytokines, production and release of cytotoxic granules, and apoptotic cell death through Fas molecules.