28/08/2024
immunity 2
From ATOM
MHC ( major Histocompatability complex) also know as HLA in human as was identified on human man leukocytes first .
Structure and Function
* The MHC has three regions: MHC-I, MHC-II, and MHC-III (Figure 1).
* The classical HLA antigens encoded in each region include HLA-A, -B, and -C in the MHC-I region, and HLA-DR, -DQ, and -DP in the MHC-II region.
* The MHC-III region includes several genes involved in the complement cascade and cytokines
* In general, when we refer to MHC, we are referring to either MHC-I or MHC-II molecules.
*
* The class I a chains consist of a single polypeptide composed of three extracellular domains named a1, a2, and a3, ONE transmembrane region that anchors it in the plasma membrane, and a short ONE intracytoplasmic tail (Figure 2).
* The b2 microglobulin consists of a single non-polymorphic molecule noncovalently bound to the alpha chain and is encoded on chromosome 15 .It joins the three alpha
* The folding of the a1 and a2 domains creates a long cleft or groove that is the site at which peptide antigens bind to the MHC-I molecule and are presented to the CD8 lymphocyte.
* MHC-II molecules consist of two polypeptide chains, a and b, both encoded in the MHC-II region on chromosome 6 and noncovalently linked to one another.
* The TWO a and b chains each consist of TWO extracellular domains referred to as a1 and a2 and b1 and b2, respectively, and, similar to the MHC-I a chain, the a and b chains of the MHC-II molecule also consist of TWO transmembrane segment and TWO cytoplas-mic tail .
Expression of MHC Molecules MHC-I
* MHC- I proteins are expressed on all nucleated cells, in contrast to MHC-II molecules, which are restricted to antigen-presenting cells (APCs)
* Lymphocytes, macrophages, dendritic cells, Langherans cells, and some endothelial cells are the predominant cells that express MHC-II.
* Nonnucleated cells such as mammalian red blood cells express little or no MHC-I and thus, pathogens within red blood cells can go undetected by cytotoxic T cells, e.g., malaria.
* The expression of both MHC-I and MHC-II molecules is regulated by cytokines.
* Interferon-g (INF-y) increases the expression of MHC-I or MHC-II molecules and can induce the expression of MHC-II molecules on certain cell types that do not normally express them. This may be very important both in normal immunologic function and in autoimmunity.
* The level of MHC molecule expression plays an important role in T cell activation and therefore differences in levels of expression are significant.
* Shown in Table 1 is a comparison of the principal differences between MHC-I and MHC-II molecules.
* TABLE 1
Polypeptide chains
A single a chain (44–47 kD) noncova-lently linked to the b2-microglobulin chain (12 kD)
A single a chain (32–34 kD) non-covalently linked to a single b chain (29–32 kD)
Distribution
All nucleated cells
Antigen-presenting cells
Composition of antigen-binding clefts
a1 and a2 domains
a1 and b1 domains
Binding site for T cell co-receptor
CD8 binds to the a3 region
CD4 binds to the b2 region
Size of peptide-binding cleft
Accommodates peptides of 8–11 residues
Accommodates peptides of 10–30 residues or more
Nomenclature in the human
HLA-A, HLA-B, HLA-C
HLA-DR, HLA-DQ, HLA-DP
Antigen Presentation
Endogenous antigens are presented via class 1 MHC to CD8 cytotoxic T cell which causes apoptosis of cells containing antigen
Exogenous antigens are presented via class 2 MHC to T helper CD 4 cells which release lymphokines that cause B cell proliferation into memory cells and plasma cells which make antibodies and also acts on CD8 T cell to make memory and attack cells against antigen leading to double attack vis T cell and antibodies.
Mohammad Uzair
