Q.17 Dendritic cells are involved in cross–presentation of antigens. Which of the
following protein(s) is(are) required for cross–presentation?
P. Basic leucine zipper ATF–like transcription factor 3 (BATF3)
Q. Membrane associated ring–CH–type finger 1 (MARCH–1)
R. Solute carrier family 10 member 1 (SLC10A1)
S. Class II–associated invariant chain peptide (CLIP)
(A) P only
(B) P and R only
(C) P, Q and R only
(D) S only
Answer: (A) P only
Dendritic cells perform cross-presentation by processing exogenous antigens for MHC class I presentation to CD8+ T cells, a key process in anti-viral and anti-tumor immunity. BATF3 drives development of specialized CD103+ and CD8α+ dendritic cell subsets essential for this pathway. Other options lack direct involvement.
Option Analysis
P. BATF3: This transcription factor is required for differentiation of cross-presenting dendritic cells. Batf3-deficient models show severe defects in cross-presentation and CD8+ T cell priming.
Q. MARCH1: This E3 ubiquitin ligase degrades MHC class II and regulates endosomal trafficking, but it inhibits rather than enables cross-presentation.
R. SLC10A1: Also called NTCP, this bile acid transporter functions in hepatocytes for viral entry (e.g., HBV), unrelated to antigen cross-presentation.
S. CLIP: This invariant chain peptide blocks MHC class II until peptide exchange; it associates with class II, not class I cross-presentation.
Dendritic cells cross-presentation of antigens activates CD8+ T cells against pathogens and tumors. In competitive exams like GATE Biotechnology 2023 Q17, candidates must identify key proteins like BATF3 required for this process.
Cross-Presentation Mechanism
Exogenous antigens enter specialized dendritic cells via endocytosis, traffic to cytosol for proteasomal degradation, and load onto MHC class I. BATF3-lineage cells (CD103+ DCs) excel here due to efficient ER-phagosome fusion and TAP transport.
Why BATF3 is Essential
BATF3 transcription factor regulates IRF8 and Id2, driving CD8α+ and CD103+ DC development. Knockout mice fail viral clearance and tumor rejection from absent cross-presentation.
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XCR1+ DCs, BATF3-dependent, show superior OT-I T cell proliferation.
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Non-lymphoid CD103+ DCs mirror splenic CD8+ DCs in function.
Other Options Incorrect
| Option | Protein | Role | Cross-Presentation Link |
|---|---|---|---|
| Q | MARCH1 | Ubiquitinates MHC II for lysosomal degradation | Downregulates surface MHC; no positive role |
| R | SLC10A1 (NTCP) | Bile acid/hepatitis B transporter | Liver-specific; irrelevant to DCs |
| S | CLIP | MHC II peptide placeholder | Class II pathway only |
Exam Relevance
GATE BT 2023 answer is (A) P only, testing immunology depth. Similar for IIT JAM Biotechnology: focus BATF3-dependent cDC1 subset in adaptive immunity.
