Differential Antigen Processing Pathways. TAP: Transporter associated with Antigen Processing...

Differential Antigen Processing Pathways

TAP: Transporter associated with Antigen Processingheterodimer

Black proteosome subunits alter catalysis to produce MHC I ready peptides

Assembly of “Loaded” MHC I requires chaperone proteins CalnexinTapasin associates with TAP to help load the peptideERp57 allows for release of the “loaded” MHC I after assembly.

Loading MHC II

Assembly of MHC II: Newly synthesized MHC binds invariant chain (prevents premature peptide binding and helps direct MHC to endocytic compartment via sorting signals). Invariant chain is degraded as the complex passes through the endocytic pathway. CLIP (Class I-associated Invariant Chain Peptide) stays bound in the peptide-binding groove.

A “non-classical” MHC II molecule, HLA-DM, catalyzes the exchange with peptides to be presented. HLA-DM is intracellular only.

Summary of antigen processing.

Only membrane bound—structural analysis tough… why?

Early T-Cell Studies

• Infect mice with lymphocytic choriomeningitis virus (LCMV)

• CTLs generated lysed infected cells• Did not react with free virus particles or

viral peptides• ??????????• Self-restriction of T-cells• Analyze TCRs by antibody

production/binding• TCRs have Variable regions and Constant

regions!!!!!!!!!!!• ISOLATE GENE

Subtractive Hybridization

Why?

98% of gene expression is the same in B and T cells

Rearranged DNA

In Ig superfamilyWhy?

Like Fab

Other TCRs are

Secondary structure?

MHC not required for recognition!More like innate immunity.Important against parasites and some bacteria.

Productive rearrangement for deletes !!

Gene rearrangements yield a functional TCR.

Rearranged genes

Unlike B-cells, T-cells do not undergo somatic mutations.

T-cell receptor Complex: TCR + CD3

and result fromdifferential RNA splicing

Immunoreceptor tyrosine-based activation motif

Ig domains

TCR accessory proteins

Coreceptor interactions