KIR3DL1 Human

Killer Cell Immunoglobulin-Like Receptor, 3 Domains Long Cytoplasmic Tail 1 Human Recombinant

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Cat. No.

BT26569

Source

Escherichia Coli.

Synonyms

Killer cell immunoglobulin-like receptor 3DL1, MHC class I NK cell receptor, Natural killer-associated transcript 3, NKAT-3, p70 natural killer cell receptor clones CL-2/CL-11, HLA-BW4-specific inhibitory NK cell receptor, CD158 antigen-like family member E, CD158e antigen, KIR3DL1, CD158E, NKAT3, NKB1, KIR, NKB1B, CD158E1, MGC119726, MGC119728, MGC126589, MGC126591.

Appearance

Sterile filtered colorless solution.

Purity

Greater than 95.0% as determined by(a) Analysis by RP-HPLC.
(b) Analysis by SDS-PAGE.

Usage

Prospec's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.

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Description

Genetic Polymorphism and Evolutionary Significance

Allelic Diversity:

Over 77 KIR3DL1 alleles identified, classified into three lineages: 3DS1-like, 005-like, and 015-like, maintained by balancing selection .
Subtypes differ in surface expression levels:

Subtype Expression Level Example Alleles
High (h) High KIR3DL1015
Low (l) Low KIR3DL1005
Null (n) No expression KIR3DL1004
Activating Activating KIR3DS1013

Subtype	Expression Level	Example Alleles
High (h)	High	KIR3DL1015
Low (l)	Low	KIR3DL1005
Null (n)	No expression	KIR3DL1004
Activating	Activating	KIR3DS1013

HLA-Bw4 Interaction:

Binds HLA-A/B alleles with the Bw4 epitope, which varies by residue 80 (isoleucine vs. threonine) :

HLA-Bw4 Subtype Interaction Strength Example Alleles
Bw4-80I Strong HLA-B*57:01
Bw4-80T Weak HLA-B*13:02

HLA-Bw4 Subtype	Interaction Strength	Example Alleles
Bw4-80I	Strong	HLA-B*57:01
Bw4-80T	Weak	HLA-B*13:02

Functional Mechanisms in Immune Regulation

Inhibitory Signaling:

Engagement with HLA-Bw4 triggers ITIM phosphorylation, recruiting phosphatases (e.g., SHP-1) to block NK cell cytotoxicity .
Peptide Sensitivity: Polymorphisms at residues 282/283 (e.g., E283) determine specificity for HLA-bound peptides, including HIV-1 antigens .

Licensing of NK Cells:

NK cells expressing KIR3DL1 are "licensed" by HLA-Bw4, enhancing responsiveness to missing-self signals .
Individuals homozygous for HLA-Bw4 exhibit stronger NK cell activation than Bw6 homozygotes .

CD8+ T Cell Modulation:

KIR3DL1+ CD8+ T cells show reduced activation (CD69/Ki67) and weaker HIV-specific responses (IFN-γ/CD107a) compared to KIR3DL1− subsets .

Clinical and Therapeutic Implications

HIV-1 Infection:

KIR3DL1high alleles (e.g., 015) with HLA-Bw4-80I correlate with delayed AIDS progression .
KIR3DL1− NK cells inversely associate with viral load set points in acute HIV infection .

Cancer Immunotherapy:

In chronic myeloid leukemia (CML), dasatinib enhances NK cytotoxicity in a KIR3DL1 allotype-dependent manner .

Table: Clinical Associations of KIR3DL1 Variants:

Condition	Key Finding	Source
HIV-1	KIR3DL1<sup>high</sup> + Bw4-80I slows progression to AIDS
CML	Dasatinib boosts NK activity against TKI-resistant cells via KIR3DL1
Hematologic cancers	KIR3DL1<sup>−</sup> NK activation predicts better prognosis

Product Specs

Introduction

Killer-cell immunoglobulin-like receptors (KIRs) are a family of proteins found on the surface of natural killer (NK) cells, which are part of the immune system. These receptors help control the NK cells' ability to eliminate other cells. KIRs do this by interacting with molecules called MHC class I, which are present on most cell types. This interaction enables KIRs to detect infected or cancerous cells that have abnormally low levels of MHC class I. Most KIRs are inhibitory, meaning they prevent NK cells from killing when they interact with MHC class I. However, a few KIRs can activate NK cells. KIR genes are located on chromosome 19q13.4 within a region called the leukocyte receptor complex (LRC). KIR genes are highly diverse, meaning individuals have different sets of KIR genes and, therefore, different KIR proteins. KIR proteins are categorized based on their structure, specifically the number of extracellular immunoglobulin domains (2D or 3D) and the length of their intracellular tail (long (L) or short (S)). KIRs with long tails inhibit NK cell activity through a motif called ITIM, while those with short tails activate NK cells by interacting with a protein called TYRO. KIR3DL1, also known as NKB1, nkat3, or p70KIR, is an inhibitory KIR that recognizes a specific region on HLA-B molecules called the Bw4 determinant. This interaction triggers the ITIMs in KIR3DL1's tail to suppress NK cell activity. This product consists of the cytoplasmic tail of KIR3DL1 (amino acids 361-444) with a His-tag, which was initially produced in E. coli as insoluble aggregates (inclusion bodies).

Description

Recombinant KIR3DL1, produced in E. coli, is a single polypeptide chain that is not glycosylated. It contains 132 amino acids and has a molecular weight of 15 kDa. The protein has been purified using proprietary chromatographic methods.

Physical Appearance

A clear and colorless solution that has been sterilized by filtration.

Formulation

The protein solution has a concentration of 1 mg/ml and is formulated in a buffer containing 25mM Tris-HCl (pH 7.5) and 100mM NaCl.

Stability

For short-term storage (up to 4 weeks), the product can be stored at 4°C. For longer periods, it should be stored frozen at -20°C. Adding a carrier protein like HSA or BSA (0.1%) is recommended for extended storage. Avoid repeatedly freezing and thawing the product.

Purity

The purity of the protein is greater than 95%, as determined by RP-HPLC and SDS-PAGE analysis.

Synonyms

Source

Escherichia Coli.

Amino Acid Sequence

MRGSHHHHHH GMASMTGGQQ MGRDLYDDDD KDRWGSTSGT IDKLDIEFHLWCSNKKNAAV MDQEPAGNRT ANSEDSDEQD PEEVTYAQLD HCVFTQRKIT RPSQRPKTPP TDTILYTELP NAKPRSKVVS CP.

Product Science Overview

Gene and Protein Structure

The KIR3DL1 gene is located on chromosome 19q13.4 within the leukocyte receptor complex (LRC), a region known for its high density of immune-related genes. The gene encodes a type I transmembrane protein consisting of 444 amino acids. The protein structure includes:

A 21-amino acid signal peptide
An extracellular region with three C2-type immunoglobulin-like domains
Three potential N-linked glycosylation sites
A 20-amino acid hydrophobic transmembrane region
An 84-amino acid cytoplasmic domain

Function and Mechanism

KIR3DL1 is an inhibitory receptor that interacts with class I major histocompatibility complex (MHC) molecules, specifically HLA-B molecules. Upon binding to its ligand, KIR3DL1 transduces inhibitory signals through immune tyrosine-based inhibitory motifs (ITIMs) present in its long cytoplasmic tail. This interaction helps regulate the activity of NK cells, preventing them from attacking normal, healthy cells.

Polymorphism and Variants

KIR3DL1 is highly polymorphic, with at least 73 known variants. These variants contribute to the diversity of the immune response among individuals. The gene is also closely related to KIR3DS1, an activating receptor with a short cytoplasmic tail. Both genes are sometimes considered alleles of the same gene due to their high sequence homology.

Clinical Significance

The polymorphic nature of KIR3DL1 has been associated with various diseases and conditions. For example, certain variants of KIR3DL1 are linked to a reduced risk of developing graft-versus-host disease (GVHD) following bone marrow transplantation. Additionally, the interaction between KIR3DL1 and its ligands has implications in the context of viral infections, such as HIV, where specific KIR3DL1-HLA combinations can influence the progression of the disease.

Research and Applications

Recombinant forms of KIR3DL1 are used in research to study its structure, function, and interactions with other molecules. These studies provide insights into the mechanisms of immune regulation and potential therapeutic targets for modulating immune responses in various diseases.

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KIR3DL1 Human

Description

Genetic Polymorphism and Evolutionary Significance

Allelic Diversity:

HLA-Bw4 Interaction:

Functional Mechanisms in Immune Regulation

Inhibitory Signaling:

Licensing of NK Cells:

CD8<sup>+</sup> T Cell Modulation:

Clinical and Therapeutic Implications

HIV-1 Infection:

Cancer Immunotherapy:

Product Specs

Product Science Overview

Quick Inquiry

Category

Service

KIR3DL1 Human

Description

Genetic Polymorphism and Evolutionary Significance

Allelic Diversity:

HLA-Bw4 Interaction:

Functional Mechanisms in Immune Regulation

Inhibitory Signaling:

Licensing of NK Cells:

CD8<sup>+</sup> T Cell Modulation:

Clinical and Therapeutic Implications

HIV-1 Infection:

Cancer Immunotherapy:

Product Specs

Product Science Overview

Quick Inquiry

Category

Service

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