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Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.
Gene References into Functions
HHLA2 protein expression was evaluated in primary tumor specimens and metastatic disease using an osteosarcoma tumor microarray. HHLA2 was expressed in almost all metastatic disease specimens and was more prevalent than in primary specimens without known metastases. PMID: 27531281
HHLA2 was not detected in most of normal lung tissue but expressed in 66% of NSCLC across different subtypes. In particular, EGFR-mutated NSCLC was significantly associated with higher tumor HHLA2 expression in both discovery and validation lung cancer cohorts. HHLA2 is widely expressed in NSCLC and is associated with EGFR mutation and high TILs in lung adenocarcinoma. PMID: 27553831
Low B7-H5 expression is associated with pancreatic adenocarcinomas. PMID: 25519928
The HHLA2 pathway represents a novel immunosuppressive mechanism within the tumor microenvironment. PMID: 25549724
B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H PMID: 23784006
Data indicate that HHLA2 protein was predominantly found on cell membranes with some in the cytoplasm. PMID: 23716685
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Subcellular Location
Membrane; Single-pass type I membrane protein.
Tissue Specificity
Expressed at high levels in colon, kidney, testis, lung and pancreas, and at lower levels in small intestine, liver and skeletal muscle. In immune cells, highly expressed in B-cells, dendritic cells and macrophages. Not detected in T-cells.
