Other immune cell membrane molecules There are many types of immune cell membrane molecules, and the classification methods have different perspectives. As mentioned earlier, CD antigens mainly use monoclonal antibodies and other technologies. The classification of cell membrane molecules that perform various functions is almost all-encompassing. In CD, actually include some Ig superfamily members, most of the adhesin superfamily members and all selectin members in the adhesion molecules. In addition, from the perspective of functional classification, cell membrane molecules also include immunocompetent cell antigen recognition receptors, major histocompatibility antigens, cytokine receptors, differentiation antigens of T and B lymphocytes, which will be described in this book Relevant chapters are elaborated separately. This section mainly introduces mitogens and their corresponding binding molecules on lymphocytes and various IgFe receptors.
1. Mitotropin receptor
Mitogen (mitogen) comes from plant protein or bacterial products, it can be combined with a variety of cell membrane carbohydrates and oligosaccharide-based molecules, the latter is to promote mitogen receptors, after binding can promote cell activation and induce cell division. Since the cell membrane contains different glycosyl groups, it can be considered as a polyclonal activator, which is different from the antigen-specific clonal activation.
Both T and B cells have mitogen receptors on their surface, which can non-specifically stimulate the transformation of resting lymphocytes into mother cells in vitro. The DNA synthesis of the transformed cells increases, and the morphological changes such as increased cell volume, increased cytoplasm, basophilism, and mitosis occur. This transformation process is very important for studying changes in lymphocyte function and biochemical changes in the early activation process of lymphocytes. This lymphocyte transformation process can be incorporated with 3H-TdR to detect changes in DNA synthesis or cell transformation by light, and is often used for T cell function testing. American Pokeweed (PWM) can induce T and B cell transformation, while bacterial lipopolysaccharide (LPS) can cause B cell transformation (Zhen 6-8).
Table 6-8 Common mitogens
Name Source Molecular Weight (kD) Sugar-specific properties and applications Concanavalin A (ConA) Concanavalin 102 α-D-mannosyl-
α-D-glucose T-cell mitogen, isolated cell membrane glycoprotein Phytohemagglutinin (PHA) Yundou 120 N-actyl-D-galactosamine T-cell mitogens Pokeweed mitogen (PNA) Pokemon 32 β-N-acetyl-D-glucosamine B cell, T cell mitogenic soy lectin (SBA) peanut 110 D-galactosyl- (β1-3) -N-acetyl-D-galactosamine isolated thymus cell subpopulation (cortex Immature thymocytes and PNA agglomerate into PNA + cells) Soybean lectin (SBA) Soybean 120 N-acetyl-D-galactosamine
D-galactose agglutinates immune active B cells and purifies human bone marrow for bone marrow transplantation
2. Ig Fe receptor
Ig is divided into five categories: IgM, IgD, IgA, IgD and IgE. The different functions of various types of Ig are mainly related to their structure. Many cells in the body have different types of IgFe receptors. Through the combination of Fe receptors and IgFe, they participate in Ig-mediated physiological functions or pathological damage. The Fe receptors that have been clearly identified are FeγR, FcαR and FcεR.
(1) FeγR
1. The structure and distribution of FeγR FeγR can be divided into three categories: FeγRâ… , FeγRâ…¡ and FeγRâ…¢. Their structure and distribution are different.
(1) FeγRâ… (CD64): a 70kD transmembrane glycoprotein, belonging to the Ig superfamily, with three C2 structures in the extracellular region. FeγRâ… is mainly distributed in monocytes, macrophages, and neutrophils. IFN-γ can stimulate the neutrophils of monocytes and macrophages to express FeγRâ… levels increased by 5 to 10 times. G-CSF also promotes this.
(2) FeγRⅡ (CD32), a 40kD transmembrane glycoprotein, belongs to the Ig superfamily. There are two C2 structures in the extracellular region. FeγRⅡ is expressed in blood cells other than red blood cells.
(3) FeγRⅢ (CD16): It is a 50-70kD glycoprotein, belongs to the Ig superfamily, and has two C2 structures. Mainly distributed on the surface of macrophages, NK cells and eosinophils, neutrophils.
2. The function of FeγR The function of FeγR is mainly exerted by myeloid cells and NK cells.
(1) Mononuclear-macrophage cells: FeγRâ… , â…¡ and â…¢ can be introduced into mononuclear fine ADCC to kill tumor and other target cells. This ADCC effect is Mg2 + dependent and requires the participation of adhesion molecules such as LFA-1. IFN-γ can promote FeγRâ… -mediated killing of monocytes. Monocyte-phagocytic cells may play a role in regulating phagocytosis and clearing immune complexes through FeγRâ… , â…¡, â…¢.
(2) Neutrophils: Freshly isolated neutrophils cannot lyse target cells through FeγR, but after IFN-γ stimulation, they can mediate cytotoxicity through FcγRâ… and FcγRâ…¡, which mainly induces increased expression levels of FcγRâ… . However, there was no change in the expression level of FcγRâ…¡, which may be regulated by the killing mechanism. GM-CSF can also significantly enhance the neutrophil killing level through FcγRâ…¡. Activated neutrophils play a role in regulating phagocytosis and clearing immune complexes through FcγRâ… and â…¡.
(3) Eosinophils: unstimulated eosinophils have no killing effect, GM-CSF, TNF and IL-5 are effective activators of eosinophils to exert ADCC effect, in anti-parasitic and anti-tumor Has an important role. GM-CSF activation is mainly mediated by FcγRⅡ.
(4) NK cells: FcγRⅢA mediates ADCC to kill tumor cells and other target cells. IL-2 and IFN-γ can significantly increase the killing activity of NK cells, but it does not significantly change the expression level of FcγRⅢ.
Other immune cell membrane molecules (2) FcαR
FcαR (CD89) is a membrane-penetrating glycoprotein with a molecular weight of 60 kD. It belongs to the Ig superfamily. There are two C2 functional regions outside the cell membrane with medium affinity. It is mainly expressed in monocytes, macrophages, and neutrophils. Guide phagocytosis, ADCC and release of inflammatory mediators.
(3) FcεR
The structure and distribution of FcεR FcεR can be divided into two categories: FcεRâ… and FcεRâ…¡. Their structure, distribution, and mediated effects are different.
(1) FcεRI: high affinity receptor, K value 10-9 ～ 10-10M. It is composed of four chains of α, β and γ-γ. FcεRâ… is mainly distributed in basophils and mast cells.
(2) FcεRII (CD23): low-affinity receptor, molecular weight 45kD, single-chain transmembrane glycoprotein. The 25kD part of the extracellular C-terminal side is also called IgE-binding factor (IgE-BF). FcεRⅡ can form soluble CD23 molecule (Scd23), ie IgE-BF, after proteolytic cleavage.
2. The function of FcεR
(1) FcεRâ… : basophils and mast cells have high affinity FcεRâ… . When the corresponding allergen is combined with basophils and mast cell surface lgE / FcεRâ… complex, the cells are degranulated, synthesized and released more A medium that mediates type I immediate hypersensitivity.
(2) FcεRⅡ: FcεRⅡ is a B cell differentiation activation antigen. In PBMC of patients with allergic diseases, CD23 density increased significantly, and serum sCD23 increased. sCD23 has BCGF activity, promotes B cells to produce IgE, and has a synergistic effect with IL-4. In addition, FcεRⅡ can also mediate IgE-dependent ADCC and phagocytosis.
3. Cytokine receptors
A variety of cytokine receptors are expressed on the surface of immune cells, and the types, density, and affinity of cytokine receptors expressed by different immune cells are different.
1. Cytokine receptors on the surface of T cells A variety of cytokines can regulate the function of T cells, because T cells have corresponding cytokine receptors, such as IL-1R, IL-2R, IL-3R, IL- 4R, IL-6R, IL-7R, IL-8R, IL-9R, IL-12R, TNF-αR, G-CSFR, TGF-βR, etc. The number and affinity of quiescent and activated T cytokine receptors can be very different. For example, quiescent T cells only express the IL-β chain, which binds to IL-2 ligands with medium affinity. When T cells are activated, they also express IL-2Rα Chain and β chain, and constitute a high affinity receptor.
2. Cytokine receptors on the surface of B cells A variety of cytokines regulate the activation, proliferation, and differentiation of B cells by binding to the corresponding cytokine receptors on the surface of B cells to play a regulatory role. The cytokine receptors of B cells mainly include IL-1R, IR-2R, IL-4R, IL-5R, IL-6R, IL-7R, IL-11R, IL-12R, IFN-γR, TNF-α and TGF -βR etc.
3. Cytokine receptors on the surface of mononuclear-macrophages There are various cytokine receptors on the surface of mononuclear-macrophages, such as MCFR, MIFR, MAFR, IFNR, M-CSFR, GM-CSFR, etc., corresponding cells After the action of the factor, it can regulate the phagocytosis function of monocyte-macrophage, cytotoxicity, the expression of MHC class II antigen and the synthesis and release of monocyte factor.
Four, sheep red blood cell receptor
There are receptors on the surface of human T cells that can bind to sheep red blood cells, called E receptors. E receptors can bind to ligands on the surface of sheep red blood cells in vitro under certain conditions, and can form a floral ring on the surface of T cells. For E garland. This method can be used to detect the relative percentage of human peripheral blood T cells and can be used as one of the indicators to judge the immune function of human T cells.
The E receptor has proved to be a glycoprotein molecule with a molecular weight of 30-60 kD. The monoclonal antibody was used to identify the E receptor, which was considered to be a new human T cell differentiation antigen, named leukocyte differentiation antigen 2 (Leu-5, OKT11, CD2). It is currently believed that the E receptor may mediate the Ca2 + -dependent T cell bypass activation pathway.
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