HHLA2 (Human endogenous retrovirus-H long terminal repeat-associating protein 2) (B7-H7)

HHLA2 (B7-H7) is a transmembrane immunomodulatory ligand of the B7 family, structurally characterized by one Ig-like C1-type and two Ig-like V-type domains[1]. It is expressed on various immune cells, including monocytes, macrophages, dendritic cells, and is inducible on B cells and exhausted T cells[1][4]. Its functions are context-dependent, capable of both stimulating and inhibiting T-cell responses through interactions with the receptor CD28H (TMIGD2), which is involved in immune activation, cell adhesion, migration, and angiogenesis[1][2][4]. HHLA2 is highly expressed in several cancers wherein its overexpression correlates with negative prognosis, making it a promising target for immunotherapeutic intervention as both a checkpoint molecule and a biomarker[4][8].

Other names

B7-H7HHLA2B7 homolog 7HERV–H LTR-associating 2B7yB7-H5 (may also refer to VISTA; usage varies)

Immune checkpoint blockade (antibodies antagonizing HHLA2 or its receptor); Modulation of T-cell costimulation (restoring T-cell activation by inhibiting the HHLA2-CD28H axis); Enhancement of antitumor immunity