System Serology Examples

Fc receptor definition

Fc receptor is a antibody receptor involved in antigen recognition which is located at the membrane of certain immune cells including B lymphocytes, natural killer cells, macrophages, neutrophils, and mast cells. Such receptors recognize Fc fragment of antibodies and that is the name of Fc receptor derived from. Fc receptors binding to antibodies that are attached to infected cells or invading pathogens contributes to the protective functions of the immune system.Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity.

Fc receptor contribution

Fc receptors are found on a number of cells in the immune system including phagocytes like macrophages and monocytes, granulocytes like neutrophils and eosinophils, and lymphocytes of the innate immune system (natural killer cells) or adaptive immune system (e.g., B cells). They allow these cells to bind to antibodies that are attached to the surface of microbes or microbe infected cells and help these cells to identify and eliminate microbial pathogens. Activation of phagocytes is the most common function attributed to Fc receptors.

Types of Fc receptor

There are several types of Fc receptors dpending on the kind of antibody that they recognize. Fc receptors recognizing fc portion of IgG is called Fc gamma receptor (FcγR). Fc receptor recognizing C-terminal of IgA is called Fc alapha receptor (FcαR). Fc receptor recognizing C-terminal of IgE is called Fc epsilon receptor (FcεR).

Types of FcyR receptors

Receptors recognizing the Fc region of immunoglobulin (Ig) G (FcγR) have attracted much interest concerning the aetiology and pathogenesis of autoimmune diseases [1, 2]. In addition to the placental FcγR (FcγRn), which transfers maternal monomeric IgG to the fetus, three distinct classes of FcγR have been characterized: FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16). Human FcγRII is divided into subclasses A, B and C, and for FcγRIII subclasses A and B have been described [3]. Except for FcγRIIB, all FcγRs are activating, e.g. they initiate antibody-dependent cellular cytotoxicity, proinflammatory cytokine secretion and phagocytosis, ultimately resulting in immune complex clearance and antigen presentation by antigen-presenting cells [4, 5]. In contrast to FcγRII and FcγRIII, FcγRI is a high-affinity receptor with the ability to bind IgG monomers

Dan's use-case:

• What’s being collected is “Antigen-specific FcR Binding” with results in units of median fluorescence intensity
• FcR is a cell surface receptor that binds to the Fc (constant domain) of an IgG antibody
• The antigens are HA’s from a variety of influenza strains
• Antigens are bound to magnetic micro beads
• Subject serum is added and antigens are bound by antibodies specific for them
• Microbeads with an antibody-antigen complex are separated from microbeads with unbound antigens
• Various FcR’s are added and incubated with the antibody-antigen microbead complexes
• The mdFI of the resulting antigen-antibody-FcR microbead complex is assessed

Since different IgG subclasses bind with different affinities to different FcR’s and different FcR’s trigger different effector responses, the results give an insight into the types of effector responses elicited towards each antigen. See, e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333794/

There’s some difficulty in modeling this since there are basically two binding targets of the antibody – 1.) the antigen via the variable region of the antibody and 2.) The Fc receptor via the constant region of the antibody. A further subtlety is that constant regions of the antibodies can bind to multiple FcR’s, so it’s not like we can say we are measuring IgG1-antigen complex (ISTEST)  binding to the FcR (ISBDAGNT). Modeled this would also mean we’d either blow ISTESTCD terminology or need a work-around such that antibody-antigen complexes could be listed in the SUPPIS.

If our end goal is to quantify the antibodies:

Questions:

1. Is this a flow cytometry test? if so, should this be handled by CP? do you need to represent info such as "activated", gating?
2. How many receptor polymorphisms are there?
3. Before we agree to map this to IS, can we try to flash out the ISTESTs as much as possible for this type of assays?