Antigens and MHC.

1. Antigens
Antigens are foreign molecules that are recognized by the immune system.
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Interaction between receptor and ligand.
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Strength of binding is important in activation.
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They can bind to antigen-specific receptors (antibodies and T cell receptors).
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Antigens that do not bind, do not induce an immune response.
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Antigens are usually proteins, peptides, polysaccharides or lipids.
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immunogen
An immunogen is an antigen that induces an immune response.
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An antigen binds the highly variable immunoreceptor products (B-cell receptor or T-cell receptor).
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hapten
Hapten is a small molecule that is antigenic but not immunogenic.
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It is univalent and must be attached to a carrier to become immunogenic.
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It is only when attached to a large carrier such as a protein
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For example, penicillin, when bound to a carrier, may activate an allergic response.
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epitope
The epitope is the part of the antigen that interacts with the antigen-specific molecules.
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They are typically 8 to 20 amino acids long, and a single protein antigen can have multiple epitopes.
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is recognized by the immune system, specifically by antibodies, B cells, or T cells.
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exogenous antigens
antigen processing cells such as macrophage and dendritic cells.
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The immune system's response to exogenous antigens is often subclinical.
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By endocytosis or phagocytosis, exogenous antigens are taken into the antigen- presenting cells (APCs) and
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processed into fragments.
examples; bacteria, viruses, fungi
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endogenous antigens
these are body's own cells or sub fragments or compounds or the antigenic products that are produced.
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are generated within normal cells as a result of normal cell metabolism, or because of viral or intracellular
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bacterial infection.
Endogenous antigens include xenogenic (heterologous), autologous and idiotypic or allogenic (homologous)
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antigens.
examples: blood group antigens, HLA(Histocompatibility Leukocyte Antigens), etc.
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Autoantigens
usually normal protein or complex of proteins that is recognized by the immune system of patients suffering
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from specific autoimmune disease.
examples: nucleoproteins, nucleic acids
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Viral antigens
For virus-associated tumors, such as cervical cancer and a subset of head and neck cancers, epitopes derived
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from viral open reading frames contribute to the pool of neoantigens
Tumor antigens
are those antigens that are presented by MHC class I or MHC class II molecules on the surface of tumor cells.
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2. Major Histocompatibility Complex
MHC is a coding region for surface proteins, such as HLA's essential for the acquired immune system to
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recognize foreign molecules in vertebrates, which in turn determines histocompatibility.
This region has been highly associated with a great many polygenic, complex diseases and character traits due
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to its extremely high level of variation within individuals compared to other areas of their genome.
Presentation of antigenic peptides
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Adaptive immune response
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T cells recognize antigen presented by MHC I or II
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CD4 binds to MHC II, CD8 binds to MHC I
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Innate immune response
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NK cells have KIR that binds to MHC I= inhibitory signal
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MHC class I
The largest region
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CD8 T cell recognize Ag/MHC class 1
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The MHC I molecule is composed of a SINGLE polypeptide chain plus non MHC protein called the beta
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microglobulin protein which is coded for at another genetic location-> SINGLE domain
>Peptide-binding groove (alpha and beta)
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Three genes that code for an MHC class I polypeptides
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>HLA-A, HLA-B, and HLA-C (HLA= Human leukocyte Antigen)
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Present processed ENDOGENOUS antigen to CD8 T Cell
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Class I including extended region
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which contains genes such as:
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HFE - causes haemochromatosis, associated with diseases such as MS
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UBD - associated with gastrointestinal malignancies
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HLA-G - associated with Pemphigus vulgaris in Jewish
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HLA-A - associated with autoimmunity
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PSORS1C1 and PSORS1C2 - associated with Psoriasis
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Classical HLA class I: HLA-A, -B, -C
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highly polymorphic and ubiquitous tissue expression
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Non classical class I: HLA-E, -F, -G
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limited polymorphism and tissue expression
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MHC class II
CD4 T cell recognize Ag/MHC class 2
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The MHC II molecule is composed of a TWO polypeptide chains: Alpha and Beta chain.
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Class II including extended region
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which contains genes such as:
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HLA-DR loci - associated with autoimmunity, particularly arthritis and diabetes
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HLA-DQ loci - associated with autoimmunity particularly narcolepsy
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BRD2 - associated with Juvenile myoclonic epilepsy
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COL11A2 - causes autosomal dominant deafness and other diseases
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TAPBP - causes bare lymphocyte syndrome type I
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Classical HLA class II: HLA-DR, -DQ, -DP
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highly polymorphic and limited tissue expression
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Non classical class II: HLA-DO, -DM
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oligomorphic, accessory molecules, not expressed on cell surface
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