W3.3 Flashcards
Major Histocompatibility Complex
”- Genetic region in humans (and other mammals) responsible for presenting antigen lymphocytes (essential to “turn on” T cells)
- Expressed in Antigen-Presenting Cells (APCs: DCs, Macs, activated B cells: MHC II) or all nucleated cells (MHC I)
Human Leukocyte Antigen
”- In humans, named human leukocyte antigen (HLA)
- HLA’s MHC molecules present both self and foreign antigens
- MHC specific to MHC “
MHC Class 1
Involved in antigen recognition (HLA-A, B, C region of chromosome)
MHC Class 2
Involved in antigen recognition (HLA-D region of chromosome: DP, DQ, DR)
MHC class 3
“Secreted proteins (area between class I and class II
- “Class III” genes:
- Complement proteins, inflammatory cytokines, protein transporters”
MHC genes
”- Most polymorphic genes present in genome
- 4000 different class I alleles and 1300 class II alleles
- MHC genes are co-dominantly expressed (both paternal and maternal genes are expressed at same level)
- Genes are so close together, they travel together during inheritance (haplotype – consists of genes for A, B, C, DR, DP and DQ)
- One haplotype inherited from each parent
- Individual’s MHC type is almost as unique as a fingerprint”
MHC Class 1 + T cells
“bind peptides within cells {of internal origin – virus/tumor} and transport/present them to the plasma membrane for recognition by CD8 T cells or cytotoxic T cells
MHC Class 2 + T cell
”- bind peptides within cells {of external sources - bacteria} and transport/present them to the plasma membrane for recognition by CD4 T cells or helper T cells
MHC Expression
”- MHC Class I found on all nucleated cells (not RBC)
- MHC Class II only found on antigen presenting cells (ex. macrophages, dendritic cells and activated B cells)
- Inflammation and adaptive responses can increase MHC expression on cells”
Structure of MHC
”- Consists of extracellular binding groove, Ig domains, and transmembrane segments and
intracellular tails
- Nearly all polymorphic sites are in or near the binding cleft
- Non-polymorphic sites in Ig domains bind CD4 and CD8 on T cells (docking mechanism)
- When no infection, MHC are filled with “self” peptides (shows cells are healthy and normal)
“
MHC Role
”- Main role is antigen presentation:
- Pick up degraded peptides within cells and present them upon transport to the plasma membrane, where T cells can then recognize them
- Difference in functioning is related to the mechanism by which the processed antigen is transported to the surface
Class 1 MCH - peptide interaction
”- MHC Class I molecules are synthesized in the endoplasmic reticulum
- Endogenous pathway of antigen presentation
Endogenous pathway
”- Antigens that bind to Class I proteins are “synthesized” in the same cell as the Class I
molecules
Self antigens or intracellular peptides such as viral particles, tumors or bacterial antigens
- Peptides that bind with Class I molecules are ~8 to 11 amino acids (derived from partial digestion of proteins synthesized in the cytoplasm)
*(CD8 T cells (cytotoxic) continuously check the cell surface for the presence of “non-self” antigen; if present T cell produces cytokines)”
Class 2 MHC - peptide interaction
”- MHC Class II molecules are synthesized in the endoplasmic reticulum
- Exogenous pathway of antigen presentation
Exogenous pathway
”- Antigen is taken into the cell from outside by means of phagocytosis or endocytosis
- Class II molecules associate with a protein called invariant chain; must be transported from the endoplasmic reticulum to an endosomal compartment to bind with the peptide
- Invariant chain: role is to prevent binding of endogenous peptides within the ER”
