Butyrophilin-like Proteins & Other Immune Checkpoint Proteins

Butyrophilin-like 2 [BTNL2]

Human immunoglobulin (Ig) superfamily receptor proteins of the structural and functional diverse butyrophilin and butyrophilin-like families, termed BTN and BTNL, are recognized as potentially important immune modulators. Butyrophilin family members have been shown to have high homology to the B7 costimulatory molecules and include molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein (MOG) and mouse Skint1 and Btnl2.

Butyrophilin-like 2 recognizes a putative receptor whose expression on B and T cells is significantly enhanced after activation. Butyrophilin-like 2 inhibits T cell proliferation and TCR activation of NFAT, NF-κB and AP-1 signaling pathways. BTNL2 is the first member of the butyrophilin family shown to regulate T cell activation, which has implications in immune diseases and immunotherapy.

LIT: Immune modulation by butyrophilins: H.A. Arnett & J.L. Viney; Nat. Rev. Immunol. 14, 559 (2014) • Novel Immune Check-Point Regulators in Tolerance Maintenance: Y. Guo & A.Y. Wang; Front. Immunol. 6, 421 (2015) • Regulation of Immunity by Butyrophilins: D.A. Rhodes, et al.; Annu. Rev. Immunol. 34, 151 (2016) 

Biologically Active BTNL2 Protein  

Other Immune Checkpoint Proteins - CD27, CD48, CD200 and CD244

Binding of CD27 [TNFRSF7], a member of the TNF receptor family, with its ligand CD70 [CD27L; TNFRSF5], results in a potent signal to activate and differentiate T cells into effector and memory cells and to boost B cells. However, despite its wide spectrum of action, this pathway has not demonstrated to be particularly effective in overcoming the immunosuppressive features of the tumor microenvironment and CD27 is considered most useful combined with other pathways.

CD48 is involved in regulating T cell activation, in cell adhesion and co-stimulation through interactions with its ligands CD2 and CD244 [2B4]. On antigen presenting cells (APCs), CD48 promotes immune synapse organization and T cell costimulation through binding to CD2 on T cells. Interactions between CD48 and CD244 regulate target cell lysis by NK cells and CTLs as well as effector and memory T cell responses. CD200 is an immune checkpoint protein related to the B7 family of co-stimulatory receptors required for T cell activation and signaling.

CD200 is expressed on the surface of tumor cells and can be released in a soluble form when cleaved by metalloproteases such as ADAM28 (A disintegrin and metalloprotease 28). Plasma levels of soluble CD200 correlate with tumor burden and survival in CLL patients. Interaction between cancer-released CD200 and its inhibitory receptor (CD200R1) on APCs suppresses secretion of pro-inflammatory cytokines, including interleukin-2 (IL-2) and interferon-γ (IFNγ) increases production of myeloid-derived suppressor cells and regulatory T cells (Tregs) and compromises an antitumor immune response. 

Biologically Active CD27, CD200 and CD244 Proteins  

VALIDATED Antibodies for CD27 and CD48 Research

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