Differential Antigen Processing Pathways

TAP: Transporter associated with Antigen Processing heterodimer

Black proteosome subunits alter catalysis to produce MHC I ready peptides

Assembly of “Loaded” MHC I requires chaperone proteins Calnexin Tapasin associates with TAP to help load the peptide ERp57 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 superfamily Why? Like F ab 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 from differential RNA splicing Immunoreceptor tyrosine-based activation motif

Ig domains TCR accessory proteins

Coreceptor interactions