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)

 

 



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)

AG-20B-0012PF

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)

ANC-121-020

All Labeled Variants

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

ANC-131-020

All Labeled Variants

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

ANC-101-020

All Labeled Variants

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

ANC-102-020

All Labeled Variants

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

ANC-144-020

All Labeled Variants

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

ANC-703-020

All Labeled Variants

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

ANC-147-020

All Labeled Variants

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

ANC-148-020

All Labeled Variants

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

ANC-704-820

All Labeled Variants

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

ANC-153-020

All Labeled Variants

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

ANC-154-020

All Labeled Variants

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

ANC-260-020

All Labeled Variants

Rat IgG2aκ FACS Mouse


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