MHC class I versus MHC class II: antigen source and T-cell partner
MHC (major histocompatibility complex) class I and class II are the main groups of cell-surface molecules that show peptides to T lymphocytes, and each class has its own T-cell partner.
Remember
CD8 and CD4 are co-receptors (surface proteins on the T cell that grip the MHC molecule): CD8+ cytotoxic ('killer') T cells read MHC class I, which usually shows peptides made inside the cell, while CD4+ helper T cells read MHC class II, which in the conventional pathway shows antigen taken up from outside the cell.
Memory aid
The rule of eight: the MHC class multiplied by the CD number gives eight.
Multiplying the MHC class by the CD number should give 8, so class I goes with CD8 (1 x 8) and class II goes with CD4 (2 x 4).
The major histocompatibility complex (MHC) is a group of cell-surface proteins that display small pieces of protein, called peptides, so that T lymphocytes can inspect them. In humans these molecules are called HLA (human leucocyte antigens). The two main classes display peptides, and the exam point is which class goes with which T cell.
MHC class I is found on almost all nucleated cells: cells with a nucleus, so not red blood cells. It usually shows peptides made inside the cell, including viral proteins. Class I being found on almost all nucleated cells makes sense, because a virus can infect any nucleated cell. Its partner is the CD8+ cytotoxic T cell, a 'killer' cell that destroys infected cells.
MHC class II is mainly on professional antigen-presenting cells (cells that take in a pathogen and display a small sample of its antigen), such as dendritic cells (the most effective antigen-presenting cells), macrophages and B cells. In the conventional pathway it shows peptides from antigen taken up from outside the cell, for example a bacterium engulfed by phagocytosis and digested into small fragments. Its partner is the CD4+ helper T cell, which coordinates the rest of the immune response, including helping B cells make antibodies.
Some antigen-presenting cells can also show extracellular antigen (antigen from outside the cell) on class I. This is called cross-presentation, and it activates CD8+ T cells, not helper cells. It exists, but it is not the conventional route for extracellular bacteria.
Key facts
- Class I location
- found on almost all nucleated cells: cells with a nucleus, so not red blood cells.
- Class I peptides and partner
- usually peptides made inside the cell, including viral proteins, shown to CD8+ cytotoxic T cells.
- Class II location
- mainly on professional antigen-presenting cells, including dendritic cells, macrophages and B cells.
- Class II peptides and partner
- in the conventional pathway, peptides from antigen taken up from outside the cell, shown to CD4+ helper T cells.
- Cross-presentation
- some antigen-presenting cells can show extracellular antigen on class I, which activates CD8+ T cells, not helper cells.
- Co-stimulation
- a naïve T cell (one that has not yet met its antigen) needs this extra activating signal as well as peptide recognition to become activated.
Exam traps
- MHC class I does not pair with CD4+ helper T cells, because CD4 helper cells recognise peptides on class II instead; class I pairs with cytotoxic CD8 cells.
- Extracellular antigen on class I with CD8+ cells is a real route through cross-presentation, but it starts a cytotoxic response, not the T helper response, which needs MHC class II and CD4+ cells.
- Detecting viral infection describes class I, which is on nearly every nucleated cell, whereas class II is mainly on specialised antigen-presenting cells.
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