MHC class I molecules present ______ antigens derived from inside the cell, then broken down and processed for presentation.
MHC class II molecules present ___ antigens derived from outside the cell, brought into the cell, then broken down and processed for presentation
Protein antigens must be broken down into small peoptides and bound to ____ for presentation to T cells
Antigen presentation by class I molecules targets cell for destruction by ____
Antigen presentation by class II molecules initiates a _____ response.
Processing of endogenous antigens occurs in the ____
Proteolysis of the endogenous protein antigens occurs via the ______
proteosome = a large protein complex in teh cytoplasm
Intracellular infection in the endogenous pathway induces the cell to produce ____
IFN-y induces the transcription of genes within the ____
Some of the IFN-y induced gene products in the MHC locus replace parts of the regular proteosome turning it into a ___
The immunoproteasome preferentially cleaves proteins after hydrophobic or basic a.a. residues, creating peptides more likely to bind to ____
class I molecules (endogenous)
In the endogenous pathway, processed peptides are located in teh ___
MHC class I proteins in the endogenous pathway are located in the ___ where the loading of the peptides occurs.
Peptides in the endogenous pathway must be translocated from the cytoplasm to the ER for loading and this occurs via ___ and ____
TAP-1 and TAP-2 (transporter associated with antigen processing)
The TAP genes in the endogenous pathway are also part of the ____ and are upregulated in the presence of ___
MHC locus and IFN-y
Human TAP preferentially binds and translocates _____
nonamerric peptides (9mers)
___ is a chaperone protein that acts to stabilize the a-chain-B2m heterodimer until a peptide is loaded and prevents the class I molecule from prematurely exiting the ER before a peptide is loaded into its peptide binding cleft in the endogenous pathway
The _____ chaperone increases the eficiency of peptide loading in the endogenous pathway.
After peptide loading in the endogenous pathway, the MHC class I peptide complex dissociates from TAP and tapasin and is transported to the cell surface via the _____
Processing of the exogenous antigens occurs within the _____ and is ____ immunity
endocytic/phagocytic vesicle; humoral
In the exogenous pathway, after a pathogen is internalized, the endosome/phagosome fuses with the ____ which contains proteases such as ____ and hydrolytic enzymes
lysosome and cathepsins
Fusion of the endosome/phagosome with the lysosome creates the ____/____.
The fused endolysosome or phagolysosome decreases resutling in proper function of enzymes which break the proteins into peptides to be loaded onto ______
MHC class II molecules
MHC class II molecules (exogenous pathway) are translated and assembled in the ____
During translation the class II molecules associate with the ____
The invariant chain binds in the ____ of the class II molecule.
peptide binding groove
What are the three functions of the invariant chain?
Act as a chaperone for proper folding of the class II polypeptides; Prevents association of the class II molecules with endogenous antigenic peptides that are in the ER that bind to class I and Helps to traffic the class II molecule to the endosomal/lysos
The class II invariant chain complex enters the ______, then exits as a membrane bound vesicle. The proteases in teh vesicle cleave the invariant chain, leavin only a small portion associated with the peptide binding cleft of the class II molecules which
golgi apparatus and CLIP ( class II associated invariant peptide)
*The vesicle containing the class II-CLIP complex fuses with the endosome/phagosome and CLIP is removed from the binding cleft by _____ and peptides are loaded onto the class II molecules. Then the class II molecule-peptide complex is transported to the
Lipid, glycolipid and phospholipid antigens can also be presented to T cells by ___ molecules. This is important in stimulating an adaptive immune response to Mycobacteria species.
CD1 molecules are similar in structure to MHC class I molecules. The binding cleft is very ____, allowing the binding of _____ lipids. The processing pathway is more similar to the _____ pathway.
hydrophobic and class II/exogenous antigen pathway.
Differences between MHC class I and II
MHC class I has a closed peptide binding groove and binds peptides 8-10 a.a. while Class II's peptide binding groove are open and binds longer peptides. MHC class I's peptides are derived from endogenous antigens where as Class II is exogenous. MHC class I's antigens are processed in cytoplasm by proteasome and class II is processed in acidic vesicles by cathepsins. Peptide loading in class I is done with TAP, Calnexin and Tapasin while in class II it's HLA-DM
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