Antigen Processing + Bare Lymphocyte Syndrome

Cytosol, vesicular

2 sources of antigen which localize to 2 different compartments

Endogenous

Compartment in cytosol

Exogenous

Compartment in vesicular/endomembrane system

Within, not, MHC I, all, proteosome, self

Endogenous Compartment

• Source is an infection __ cell (i.e. virus, self proteins, tumor cell proteins)

• __ (is/not) taken up by phagocytosis

• Fragments/peptides bind to __ _ (R)

  • Meaning occurs in __ (some/all) cells

• Proteins degraded by __

• Does include __-proteins

Phagocytosis, MHC II, phagolysosome

Exogenous Compartment

• Proteins from pathogens taken up by __ in APCs

• Fragments/peptides bind to __ __ (R)

• Proteins degraded in __

MHC I, ER, cytoplasm, lumen of ER, cell surface

Endogenous peptides and MHC I

• __ _ synthesized on ribosomes bound to ER

  • Translocated into lumen of __ as synthesized

• Small fragments of antigen/peptide are produced in __ and must be transported from cytosol into ER

• Peptide antigen and MHC I protein attach in __ of __

  • Then transported to __ __ as unit

Proteasome, TAP, Tapasin

How small fragments of antigen are retrieved in cytoplasm (via 3)

Proteasome

Break down large proteins into peptide fragments

Transporter Associated with Antigen Processing (TAP)

Located in ER membrane and moves peptides into the lumen

Tapasin

Chaperone protein bridging MHC I molecules with the TAP transporter

Endosomes and lysosomes

MHC II binds peptides generated in.. (2)…

CIITA

Gene regulating transcription of MHC II

Ribosomes, ER membrane, invariant

• MHC II polypeptides synthesized on membrane-bound __ and inserted into the __ __

• __ chain is placeholder for antigenic peptide and hold MHC together until peptide is loaded

Invariant chain

Polypeptide that blocks binding to peptide-binding groove of MHC II during transport

CLIP

Remainder of invariant chain that blocks peptide binding in last stages

DM

Another protein facilitating release of CLIP and replacement by true antigenic peptide derived from antigen

Cross-Presentation

Exogenous antigens taken up by phagocytosis presented on MHC I in APCs

Dendritic cells

…. are key cells involved in cross-presentation with APCs and MHC I

CD8, APCs

Cross Presentation

• Necessary for activation of __ T cells

  • __ are required to activate all naive T cells (including CD8s)

Bare Lymphocyte Syndrome

MHC I or MHC II deficiency from lack of expression

Genetic, processing, presentation

In bare lymphocyte syndrome:

This is a __ problem is in regulation of expression involved in antigen __ and __

Human Leukocyte Antigen

Gene complex for MHC molecules