HOPX
Overview
HOPX (Homeodomain-Only Protein X) is an atypical homeodomain protein that functions as a transcriptional regulator. In T cell biology, HOPX marks terminally differentiated effector and cytotoxic T cell populations. In the context of dengue, HOPX expression defines the cytotoxic Tph subcluster — a GZMB⁺ subset of CXCR5⁻PD-1⁺ peripheral helper T cells that is functionally distinct from the IL-21⁺ B cell help-competent Tph subset.
Key Points from Literature
- HOPX marks cytotoxic Tph in acute dengue: scRNA-seq of 4,361 activated CD4⁺ T cells from acute dengue patients identified a cytotoxic Tph cluster expressing HOPX, GZMB (granzyme B), NKG7, and KLRB1. This cluster is distinct from the IL-21⁺ helper Tph cluster (ICOS, MAF, TOX2) by gene expression and largely by TCR clonotype (only 13 shared clonotypes) (see Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue, 10x Genomics scRNA-seq + scTCR-seq, n=4 patients).
- Functional role unclear: Whether the GZMB⁺HOPX⁺ Tph subset directly kills target cells, regulates the B cell response, or contributes to immunopathology in dengue is not addressed. HOPX expression is associated with cytotoxic effector memory differentiation in CD4⁺ T cells (see Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue).
Contradictions & Debates
None documented in current wiki sources.
Related Pages
Peripheral Helper T Cell, TOX2, PD-1