Antigen processing present
Antigen processing and presentation is the step where innate detection becomes adaptive immunity. Dendritic cells capture antigen from dying tumour cells, apoptotic bodies, virus-infected debris and immune complexes through CLEC9A/DNGR-1, DEC-205, Langerin, CD206, DC-SIGN, FcγRI/FcγRII/III, CD36, LOX-1 and αvβ5, while HMGB1, HSP70, GRP94 and ecto-calreticulin plus TLR3, TLR4 and TLR9 licence maturation. Endogenous and cross-presented proteins are ubiquitinated and degraded by the 26S proteasome — switched by IFN-γ to the immunoproteasome (PSMB8/LMP7, PSMB9/LMP2, PSMB10/MECL-1) with the PA28 activator and TPP2 — then pumped by TAP1/TAP2 into the ER, trimmed by ERAP1 and ERAP2, and loaded onto MHC class I by the peptide-loading complex (tapasin, ERp57, calreticulin, calnexin, β₂-microglobulin). In parallel, the invariant chain (CD74) escorts MHC class II to the MIIC, where cathepsin S/L, legumain, GILT and the v-ATPase trim it to CLIP and H2-DM catalyses peptide exchange. Cross-presenting cDC1s (XCR1+ CD103+, driven by BATF3/IRF8) route phagosomal cargo through Sec22b/SNAP23, NOX2-controlled pH, IRAP and p97/VCP onto MHC-I. IFN-γ–JAK1/JAK2–STAT1–IRF1 drives CIITA and NLRC5 to raise both loci, while MARCH1, SOCS1, IL-10 and PD-L1 restrain the synapse. Click any protein for the matching Assay Genie In Vivo antibody or ELISA kit.
Antigen capture and dendritic-cell licensing. Conventional type 1 dendritic cells (cDC1: XCR1+, CD103+, CD11c+, specified by BATF3 and IRF8 downstream of Flt3L) are the professional cross-presenting subset. They sample dying cells through CLEC9A/DNGR-1 (which reads exposed F-actin on necrotic cargo), DEC-205/CD205, Langerin/CD207, the mannose receptor CD206, DC-SIGN/CD209, the scavenger receptors CD36 and LOX-1, the integrin αvβ5, and the Fcγ receptors CD64 and CD16/CD32 for IgG immune complexes. Released HMGB1, HSP70, GRP94/gp96 and surface-exposed calreticulin act as immunogenic-cell-death signals, and TLR3 (poly(I:C)), TLR4 (LPS) and TLR9 (CpG DNA) mature the cell through MyD88, IRF3 and NF-κB, driving CCR7-dependent migration to the draining node together with CD83, CD80, CD86, CD40 and CD70.
The MHC class I pathway. Cytosolic and defective ribosomal products are polyubiquitinated by E3 ligases and fed to the 26S proteasome. Interferon exposure replaces the constitutive catalytic subunits with PSMB8 (LMP7), PSMB9 (LMP2) and PSMB10 (MECL-1) and adds the PA28/PSME1 activator, producing peptides with C-termini favoured by TAP; TPP2 trims oversized fragments. TAP1/TAP2 translocate peptides into the ER, where the peptide-loading complex — tapasin, ERp57 (PDIA3), calreticulin and calnexin — holds the MHC-I heavy chain–β₂-microglobulin dimer open while ERAP1 and ERAP2 trim the N-terminus to an optimal 8–10-mer. Stable complexes leave via the secretory route to the surface, where H-2Kb and H-2Kd engage the CD8 co-receptor and the TCR–CD3 complex, firing Lck, ZAP-70 and LAT.
The MHC class II pathway. Newly made MHC-II αβ dimers are chaperoned by the invariant chain CD74, which blocks the groove and directs the complex to the MHC class II compartment (MIIC). Acidification by the v-ATPase licenses cathepsin S, cathepsin L, cathepsin D and legumain/AEP to degrade CD74 down to CLIP, while GILT (IFI30) reduces disulphide bonds in the antigen. H2-DM then catalyses CLIP release and edits the repertoire toward high-affinity peptides. Autophagy (LC3B, ATG5, ATG7) and the Rab5/Rab7/Rab11 endosomal machinery deliver cytosolic and recycled cargo into the same compartment. Loaded MHC-II reaches the surface for the CD4 T cell, unless MARCH1 ubiquitinates it for lysosomal degradation.
Cross-presentation and the In Vivo opportunity. Exogenous antigen reaches MHC-I by two routes: a cytosolic route in which p97/VCP retrotranslocates cargo for proteasomal processing, and a vacuolar route in which IRAP/LNPEP trims peptides directly inside the phagosome. Sec22b–SNAP23 delivers ER-Golgi machinery to the phagosome and NOX2 (with p47-phox/NCF1) keeps the lumen alkaline to limit destruction, with Rab34 controlling maturation. Transcriptionally, IFN-γ–IFNGR1–JAK1/JAK2– STAT1–IRF1 induces CIITA (the master class II transactivator) and NLRC5 (the class I transactivator), while SOCS1, IL-10, MARCH1, PD-L1 and CTLA-4 restrain the output. Because so much of this axis is receptor- and cytokine-based, it is directly addressable in vivo: anti-MHC-I (H-2Kb, H-2Kd), anti-MHC-II (M5/114), anti-CD40 (FGK4.5), anti-CD80, anti-CD86, anti-CD28, anti-CTLA-4 (9D9), anti-PD-1 (29F.1A12), anti-PD-L1 (10F.9G2), anti-CD4 (GK1.5), anti-CD8 (Ly-2), anti-CD3 (145-2C11), anti-CD11c, anti-CD103 (M290), anti-CD209b, anti-CD1d (19G11), anti-IFN-γ, anti-IFNAR-1, anti-CD70 and anti-IL-10 all perturb it, while ELISA kits quantify every processing enzyme, chaperone and transcription factor. For research use only; not for diagnostic or therapeutic procedures.
Every protein node links to a product — In Vivo antibody, ELISA kit or research antibody.