Chapter 6- BOOK - Antigen presentation to T lymphocytes

Can T cells recognize native antigens?

ONLY antigens that are displayed by MHC complexes on cell surfaces

Antigen processing

Generation of peptides from native proteins

Antigen presentation

Peptide display at the cell surface by the MHC molecule

MHC c 1

Expressed on by nearly all somatic cells (except red)

MHC c 2

Expressed primarly on cells of the immune system ex dendritic cells, macrophages, B cells…

CD4 T cells recognize peptides presented by cells in thymus

Need to be activated into effector cells before action

Cytosolic pathogen presentation

Virus + bacteria→ replicate in cytosolic compartment

Antigens are presented on MHC class 1 to activate killing by cytotoxic CD8 T cells→ cell death

Intravesicular pathogens

In vesicles→ taken up by engulfment→ killed and degraded→ presented on MHC class 2→ activate CD4 cells

Extracellular pathogen/toxins

Bind cell surface R→ endocytosis→ peptides presented on MHC class 2→ helper T cells→ B cell produce antibody

Presentation of peptides on MHC c 2

Dendritic, macro, B cells

Capture exogenous proteins→ vesicles→ Receptors→ presents on MHC→ activate CD4 T cells

Cytosolic proteins→ubiquitous pathway→ autophagosome→ CLIP → present on MHC class 2

Cytosolic degradation

Carried out by proteasome→ degradation to peptide fragments

Process is called ubiquitination→ responsible for generating majority of MHC c 1 peptides

TAP

Involved in the presentation of MHC class 1 molecules

Transports peptides from cytosol to ER

Important protein for the antigen presentation

Peptide transporter

ER

MHC class 1 molecules need to bind the peptide before it is released from ER to be transported to the cell surface

MHC class 2 pathway

Peptides are generated in acidified endocytic vesicles from proteins obtained through encocytosis, phagocytosis, autophagy

1. Antigen is taken up

2. Acidification of vesicles→ degradation into peptide fragments

3. Fuse with vesicle containing MHC class 2 molecules

4. Cell surface

Invariant chain in the MHC class 2 pathway

The invariant chain directs newly synthesized MHC class2 molecules to acidified intracellular vesicles

To prevent premature binding of peptide and MHC→ the invariant chain is expressed. → binds the groove of MHC→ cleaved in acidified endosome→ short peptide fragment, CLIP→ blocks binding of peptide→ peptide loading → CLIP is released→cell surface

Function of MHC

To bind peptide fragments derived from pathogens and display them on cell surface for recognition by the appropriate T cells

Properties of MHC

1. MHC is polygenic→ it has several MHC class 1 and 2 genes → every individual possesses a set of MHC class 1 and 2 genes with DIFFERENT ranges of peptide binding specificities

2. Polymorphic→ multiple variants, or alleles of each gene within the population as a whole, more than 1000 alleles→ spread is limited

   RESULT: Ability of the immune system to respond to multitude of different pathogens

HLA genes

Gene conversion

contributes to create new alleles by copying sequences from one MHC gene to another

Recognition of nonpeptide ligands

By T cell subsets → Non classical MHC Ib

One type: CD1→ Lipid based antigens presented to NKT cells