MHC Flashcards
B cell receptors recognize
Free antigen
T cell receptors recognize
antigen presented by MHC on cell
surface
Antigen processing
Antigen proteins digested in the cells.
Three MHC classes (I, II and III).
MHC I and II - related by structure and function. Class III is very different- (complement and TNF, lymphotoxin)
MHC class I – peptide interaction
MHC I found on all nucleated cells
Present peptides to CD8 T cells
Short peptides- 8-10 aa most are nonamers (9)
Peptides derived from the cell- endogenous antigens
Viruses or proteins from the cell
MHC class II – peptide interaction
Restricted expression- on antigen presenting cells (APC), B cells, dendritc cells, monocytes, macrophages
Present peptides to CD4 T cells Longer peptides- 13-18 aa
Peptides from antigens taken up by the cell- exogenenous antigens
Groove is open on both sides- allowing some longer peptides to
bind
Human leukocyte antigen complex
HLA
MHC class III.
Diverse set of proteins, some of them are immune system proteins, do not present antigens to T cells. Complement components, and tumor necrosis factors
Non-classical
MHC genes:
E,G,F Restricted tissue or developmental stage expresssion, varied roles in immunity. DM- role in
peptide loading of MHC class II. HLA G important for protect fetus from beeing rejected by mother
MHC genes
highly polymorphic
Variations affect antigen-binding part MHC
(polymorphic antigen binding site)
Transplant rejections
are caused by differences at MHC locus between donor and recipient
histoincompatibility
the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC).
Foreign peptides in MHC class I
targetet by CD8+ cytotoxic T cell-mediated destruction.
Target cell
The cell with foreign peptide
MHC class II molecules display
peptides from the extracellular sources Specialized cells have this function (APC, antigen-presenting cells)
CD4+ TH cells are activated
help CD8 T etc
pAPCs
Professional antigen presenting cells
Professional antigen presenting cells
dendritic cells, macrophages, B lymphocytes
dendritic cells
Express high levels of MHC class II molecules and have co-stimulatory activity all the time, and quickly activate the T cells
Macrophages
need to be activated to express MHC class II molecules and costimulatory molecules (CD80/86)
B lymphocytes
Always express low levels of MHC class II molecules; BCR catches antigen to be presented by B cell
activation occurs after interaction with pathogens via BCR and cytokine signalling, leading to MHC class II expression
Nonprofessional APC can exceptionally express MHC class II molecules:
*skin fibroblasts, thymic epithelial cells;
*glial cells, intraepithelial lymphocytes; *pancreatic beta cells, vascular endothelial cells.
Human cytomegalovirus, hepatitis B virus, adenovirus 12 interfere with MHC class I molecules
prevent CD8+ T cell activation
MHC restriction
refers to the fact that a T cell can interact with a self-major histocompatibility complex molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule.
CD4+ and CD8+ T cells can
recognize antigen only when it is presented in a groove of an MHC
Endogenous antigenes are
processed inside the cells and presented via MHC class I
Exogenous antigenes
are taken by endocytosis and presented via MHC class II
Peptides are generated by protease complexes called
proteasomes
Ubiquitin
proteinsareusedto“tag” intracellular proteins for constitutive proteasome degradation
immunoproteasome
cleaves ubiquitinated proteins into fragments that pair better with MHC molecules
Antigens enter the APCs by
Phagocytosis (cell eating)
*Endocytosis: specific B-cell receptor mediated * pinocytosis, unspecific cell drinking
Endogenous antigens –>
MHC class I –> CD8+ T cells
Exogenous antigens –>
MHC class II –> CD4+ T cells
not explained mechanistically yet
Influenza virus proteins in pAPCs are associated MHC class II and activate CD4+ T cells
b) autophagy of cytosolic components presented with MHC class II
c) cross presentation- exogenous antigens presented on MHC class I
