1. MHC Class I and
Mohammed Fareed Faizal
2. What are MHC Molecules?
• Major Histocompatibility Complex molecules
• Found along with Antigen Presenting Cells (APCs)
• These antigen pieces, or antigenic peptides, are held within the binding groove of a cell- surface protein
called the major histocompatibility complex (MHC) molecule.
• MHC molecules are encoded by a cluster of closely associated genes collectively called the MHC locus,
or simply the MHC.
• The peptide fragments that bind to MHC molecules are generated inside the cell following antigen
digestion, and the complex of the antigenic peptide plus MHC molecule is transported to the cell surface.
• Act as cell-surface vessels for holding and displaying fragments of antigen so that approaching T cells can
engage with these molecular complexes via their T-cell receptors
3. Classes of MHC Molecules
• There are three classes of MHC molecules: class I, class II, and class III.
• Members of the first two classes have a similar shape and both are responsible for displaying antigen
to T cells, although they differ in their roles and in the way in which their quaternary or final three-
dimensional structures are generated.
• MHC class I molecules and MHC class II molecules are membrane-bound glycoproteins that are
closely related in both structure and function
• These membrane glycoproteins function as highly specialized antigen-presenting molecules with
grooves that form unusually stable complexes with peptide ligands, displaying them on the cell surface
for recognition via T-cell receptor (TCR) engagement.
5. Antigen Processing and Presentation
•Antigen processing is a metabolic process that digests the proteins into peptides which can
be displayed on the cell membrane together with a class-I or class-II MHC molecules and
recognized by T-cells.
•Antigen presentation is the process by which certain cell in the body especially antigen
presenting cells (APCs) express processed antigen on their cell surface along with MHC
molecules in the form recognizable to T cell.
•If antigen is presented along with class-I MHC molecule, it is recognized by CD8+ Cytotoxic T-
cell and if presented along with class-II MHC molecule, it is recognized by CD4+ Helper T-cells.
7. Cytosolic pathway of antigen
processing and presentation
•Cytosolic pathway processed and presented the endogenous antigens i.e. those generated
within cell eg. Viral infected cells, tumor cells and intracellular pathogens (M. tuberculosis,
•The processed antigen is presented on the cell membrane with MHC-class I molecule which is
recognized by CD8+ Tc-cell for degradation.
8. Steps involved in cytosolic pathways
•Proteolytic degradation of Ag (protein) into
•Transportation of peptides from cytosol to RER
•Assembly of peptides with class I MHC molecules
9. Endocytic pathway of antigen
processing and presentation
•The endocytic pathway processed and present the exogenous Ag. i.e. antigens generated
outside the cells. E.g. Bacteria.
•At first APC phagocytosed, endocytosed or both, the antigen.
•Macrophage and dendritic cells internalize the antigen by both the process.
•While other APCs are non-phagocytic or poorly phagocytic. E.g. B cell internalize the antigen
by receptor mediated endocytosis.
•Then antigen is processed and presented on the cell surface along with class-II MHC
molecules which are recognized by CD4+ TH cell.
10. Steps involved in endocytic pathway
•Peptide generation from internalized molecules (Ag)
in endocytic vesicles.
•Transport of class-II MHC molecule to endocytic
•Assembly of peptides with Class-II MHC molecules.
The MHC got its name from the fact that the genes in this region encode proteins that determine whether a tissue transplanted between two individuals will be accepted or rejected.
Although both T and B cells use surface molecules to recognize antigen, they accomplish this in very different ways. In contrast to antibodies or B-cell receptors, which can recognize free antigen, T-cell receptors only recognize pieces of antigen that are first positioned on the surface of other cells. These antigen pieces, or antigenic peptides, are held within the binding groove of a cell- surface protein called the major histocompatibility complex (MHC) molecule. MHC molecules are encoded by a cluster of closely associated genes collectively called the MHC locus, or simply the MHC. The peptide fragments that bind to MHC molecules are generated inside the cell following antigen digestion, and the complex of the antigenic peptide plus MHC molecule is transported to the cell surface. MHC molecules thus act as cell-surface vessels for holding and displaying fragments of antigen so that approaching T cells can engage with these molecular complexes via their T-cell receptors
Other molecules classified as MHC class III also play roles in the immune response, although these roles are more varied and generally do not involve direct presentation of antigen fragments to T cells.
In order to be capable of engaging the key elements of adaptive immunity (specificity, memory, diversity, self/nonself discrimination), antigens have to be processed and presented to immune cells. Antigen presentation is mediated by MHC class I molecules, and the class II moleculesfound on the surface of antigen-presenting cells (APCs) and certain other cells.
MHC class I and class II molecules are similar in function: they deliver short peptides to the cell surface allowing these peptides to be recognised by CD8+ (cytotoxic) and CD4+ (helper) T cells, respectively. The difference is that the peptides originate from different sources – endogenous, or intracellular, for MHC class I; and exogenous, or extracellular for MHC class II. There is also so called cross-presentation in which exogenous antigens can be presented by MHC class I molecules. Endogenous antigens can also be presented by MHC class II when they are degraded through autophagy.