LAG-3 – Major Histocompatibility Complex (MHC) – T Cell Receptor (TCR) Pathway

LAG-3 and FGL-1

Lymphocyte-activation gene 3 (LAG-3; CD223) binds to major histocompatibility complex (MHC) class II molecules and functions as an immune checkpoint receptor expressed on the surface of both activated cytotoxic T cells and regulatory T cells (Tregs). LAG-3 negatively regulates T cell proliferation and the development of lasting memory T cells. LAG-3 synergizes with PD-1 in suppressing autoimmunity, tumor immunity and infection immunity and can also trigger the immunosuppressive activity of Tregs. Increased LAG-3 expression has been associated with poorer prognosis in multiple tumor types. Dual inhibition of LAG-3 and other checkpoint pathways may synergistically increase T cell antitumor activity.

New studies revealed how LAG-3 inhibits the activation of T cell response. It does not recognize MHC class II universally, but instead recognizes selectively MHC class II proteins presenting only stably bound peptides. In addition, the same study shows that LAG-3 does not compete CD4 for MHC-II interaction, but it blocks T cells by transducing inhibitory signals via its intracellular region. This recent study gives a new view on LAG-3 that might function more selectively than previously thought and probably acts to maintain immune tolerance to dominant autoantigens.

LAG-3, FGL-1, MHC and TCR Pathway

In addition, Fibrinogen-like Protein 1 (FGL1), a molecule secreted by the liver and pancreas, was identified as a major ligand for LAG-3 in both human and mouse. FGL1 binding to LAG-3 inhibits T cell response. FGL1 is upregulated in human cancers and high plasma FGL1 levels are associated with poor clinical outcome in patients treated with anti-PD1 therapy.

LIT: The CD4-like molecule LAG-3, biology and therapeutic applications: S. Sierro, et al.; Expert Opin. Ther. Targets 15, 91 (2011) • LAG-3 in Cancer Immunotherapy: M.V. Goldberg & C.G. Drake; Curr. Top. Microbiol. Immunol. 344, 269 (2011) • The promising immune checkpoint LAG-3: from tumor microenvironment enes Cancer 9, 176 (2018) • LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII: T. Maruhashi, et al.; Nat. Immunol. 19, 1415 (2018) • Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3: J. Wang, et al.; Cell 176, 334 (2019)



NEW: FGL1 (human) ELISA Assays  - Biomarker for Immuno-Oncology 

FGL1-LAG-3 interaction blockade promotes tumor immunity by stimulating T cell expansion and activation. FGL1 is highly produced by human cancer cells, and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/ B7-H1 therapy.

The FGL1 (human) ELISA Kit (Prod. No. AG-45B-0022) is a sandwich ELISA assay for specific quantitative determination of human FGL1 in serum, plasma and cell culture supernatant. This ELISA Kit shows a very high specificity and sensitivity (1.8pg/ml). The ELISA Kit contains all major components and is provided with a pre-coated 96 well plate.

In addition, we also offer the FGL1 (human) Matched Pair Detection Set (Prod. No. AG-46B-0013). This is a sandwich ELISA assay for specific quantitative determination of human FGL1 in serum, plasma and cell culture supernatant as well. The detection set leaves the research freedom to experiment and the set contains sufficient materials to run ELISAs on 5 x 96-well plates. However, the customer has to coat the plates and additional lab work has to be performed in contrary to the ready-to-use ELISA Kit. 

Biologically Active
 LAG-3 and FGL1 Proteins

Product Name PID Source Endotoxin Species
NEW Fc (human):FGL1 (mouse) (rec.) AG-40B-0185 HEK 293 cells <0.01EU/µg Mouse
NEW FGL1 (human) (rec.) (His) AG-40B-0186 HEK 293 cells <0.01EU/µg Human
NEW Fc (human):FGL1 (human) (rec.) AG-40B-0184 HEK 293 cells <0.01EU/µg Human
LAG-3 (mouse):Fc (mouse) (rec.) AG-40B-0039 CHO cells <0.01EU/µg Human, Mouse
LAG-3 (human):Fc (human) (rec.) AG-40B-0031 CHO cells <0.001EU/µg Human, Monkey, Mouse
LAG-3 (human):Fc (human) (rec.) CHI-HF-210LAG3 CHO cells <0.005EU/µg Human

VALIDATED Antibodies for LAG-3 Research


Product Name PID Isotype Applications Species
LAG-3, mAb (blocking) (11E3) (PF) AG-20B-0011PF Mouse IgG1 FUNC, ICC, IHC, IP, WB Human, Monkey
LAG-3 (human), mAb (blocking) (17B4) (PF)


All Labeled Variants

Mouse IgG1 FACS, FUNC, ICC, IHC, IP, WB Human
LAG-3 (human), mAb (AG-IHC103) AG-20B-6023 Mouse IgG1 IHC Human
MHC Class I (human), mAb (3F10)


All Labeled Variants

Mouse IgG2a ELISA, FACS, IHC Human
MHC Class II (human), mAb (TDR31.1)


All Labeled Variants

Mouse IgG1 FACS, IHC, WB Human
TCR Cβ1 (human), mAb (Jovi-1)


All Labeled Variants

Mouse IgG2a FACS Human
TCR Vβ3 (human), mAb (Jovi-3)


All Labeled Variants

Mouse IgG2aλ FACS Human
CD3 (human), mAb (UCHT1)


All Labeled Variants

Mouse IgG1 FACS, WB, FUNC Human
CD3 (mouse), mAb (145-2C11)


All Labeled Variants

Hamster IgG FACS, IP, WB Mouse
CD4 (human), mAb (QS4120)


All Labeled Variants

Mouse IgG1κ FACS, FUNC Human
CD4 (human), mAb (M-T441)


All Labeled Variants

Mouse IgG2b FACS Human, Monkey
CD4 (mouse), mAb (GK1.5) (PF)


All Labeled Variants

Rat IgG2bκ FACS, FUNC, IHC, IP Mouse
CD8 (human), mAb (UCHT4)


All Labeled Variants

Mouse IgG2a FACS, ICC, WB Human
CD8 (human), mAb (14)


All Labeled Variants

Mouse IgG1κ FACS Human
CD8-α (mouse), mAb (53-6)


All Labeled Variants

Rat IgG2aκ FACS Mouse

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