Recombinant Human HAVCR2 produced in Sf9 Baculovirus cells is a single, glycosylated polypeptide chain containing 423 amino acids (aa 22-202) and having a molecular mass of 47.3kDa. (Molecular size on SDS-PAGE will appear at approximately 40-57kDa). HAVCR2 is fused to a 239 amino acid hIgG-His-tag at C-terminus & purified by proprietary chromatographic techniques.
ADLSEVEYRA EVGQNAYLPC FYTPAAPGNL VPVCWGKGAC PVFECGNVVL RTDERDVNYW TSRYWLNGDF RKGDVSLTIE NVTLADSGIY CCRIQIPGIM NDEKFNLKLV IKPAKVTPAP TRQRDFTAAF PRMLTTRGHG PAETQTLGSL PDINLTQIST LANELRDSRL ANDLRDSGAT IRIGLEPKSC DKTHTCPPCP APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSRDELTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGKHHH HHH.
HAVCR2 was first described in 2002 by Vijay Kuchroo and colleagues during a screen to identify differentially expressed molecules between Th1 and Th2 cells . It is a cell surface molecule expressed on IFNγ producing CD4+ Th1 and CD8+ Tc1 cells . The protein plays a critical role in modulating both innate and adaptive immune responses . It is generally accepted to have an inhibitory function, although some reports suggest that its activity may be influenced by the cellular context and the respective ligand .
HAVCR2 belongs to the TIM family of cell surface receptor proteins. These proteins share a similar structure, with an extracellular region consisting of a membrane-distal single variable immunoglobulin domain (IgV), a glycosylated mucin domain of variable length located closer to the membrane, a transmembrane region, and an intracellular stem . The IgV domain is formed by two antiparallel beta sheets linked by disulfide bridges between four conserved cysteines . The extracellular portion of the IgV domain may also be glycosylated, and this glycan-binding site is recognized by the carbohydrate domain of ligands such as galectin-9 (Gal-9) .
HAVCR2 is a critical negative regulator in the immune system, acting as a negative checkpoint in peripheral tolerance and innate immune and inflammatory responses . It regulates macrophage activation and inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses, promoting immunological tolerance . The receptor is expressed by a wide range of cells, including T lymphocytes, innate immune cells such as monocytes, natural killer (NK) cells, and dendritic cells (DC), as well as cancer stem cells .
HAVCR2 has been successfully targeted to treat several solid and hematogenous malignancies, including melanoma, acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS) . Its role as a checkpoint inhibitor makes it a valuable target in cancer immunotherapy, similar to other checkpoint inhibitors such as PD-1 and CTLA-4 .
The human recombinant form of HAVCR2, produced in Sf9 cells, is used in various research and clinical applications. Sf9 cells, derived from the fall armyworm Spodoptera frugiperda, are commonly used in the baculovirus expression system for producing recombinant proteins. This system allows for high-level expression and proper post-translational modifications, making it suitable for producing functional recombinant proteins.