Cell Receptors

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CD1

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Involved in presentation of antigens to T cells, but the antigen binding groove is to some extent covered over, contains mainly hydrophobic amino acids, and is accessible only through a narrow entrance. Generally present lipids or glycolipids. CD1a, b, and c are present on cortical thymocytes, dendritic cells, and a subset of B cells. CD1d is expressed on intestinal epithelium, hepatocytes and all lymphoid and myeloid cells. Utilizes b2-microglobulin.

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CD11b

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Highly expressed integrin on APCs. CD11b deficiency worsens the inflammation and disease progression in several autoimmune disease models, but it does not affect immune activation or antigen-specific immune responses. It is involved in oral tolerance. CD11b -/- mice fed low doses of OVA and then challenged in the footpad with OVA + CFA developed strong DTH responses, unlike their WT counterparts. It is involved in IL17 suppression. Under the same tolerizing conditions as above, CD11b-/- mice developed increased numbers of Th17 cells and IL-17 production.

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CD14

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Scavenger molecule for LPS (endotoxin). Captures the complex of reactive lipid A moiety of LPS and a plasma LPS-binding protein. Once captured, TLR4 is activated, culminating in the release of NFkB and activation of transcription factor for cytokines and interferons

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CD207

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Langerin. C-type lectin that is specifically expressed on the surface of LCs and in LC-specific intracellular organelles known as Birbeck granules

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FcERI

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Fc immunoglobulin E receptor. High affinity IgE receptor. Present on mast cells. Cross-linkage leads to a number of distinct signaling steps that involve calcium influx and activation of MAPK in a PKC dependent or independent manner (Zhang 1997; Kawakami 1998). A complex containing a ligand-binding  chain structurally related to those of the FcR, a  chain, and the FcR-chain dimmer. Contact with antigen leads to degranulation of the mast cells with release of preformed vasoactive amines and cytokines, and the synthesis of a variety of inflammatory mediators derived from arachidonic acid.

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FcGRI

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CD64. High affinity for monomeric IgG. Unusual in that it has three extracellular Ig-like domains in its ligand-binding chain, while all other Fc receptors have two. Constitutively present on monocytes, macrophages, and dendritic cells, and is induced on neutrophils and eosinophils following their activation by IFNy and G-CSF. Can be downregulated in response to IL-4 or IL-13. Consists of an IgG-binding a chain and a g chain homodimer containing ITAMs. It binds monomeric IgG to the surface of the cell thus sensitizing it for subsequent encounter with antigen. Main roles are probably in facilitating phagocytosis, antigen presentation, and in mediating extracellular killing of target cells coated with IgG (ADCC).

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FcGRII

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CD32. Binds very weakly to monomeric IgG, but with considerably enhanced affinity to associated IgG as in immune complexes or on an antibody-coated target cell. Cells bearing it are therefore able to bind antibody-coated cells in the presence of high serum levels of monomeric IgG. There are multiple forms that are collectively expressed on the surface of most types of leukocytes (monocytes, macrophages, neutrophils, platelets, Langerhans cells).

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FcERII

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CD23. Low-affinity IgE receptor. C-type lectin. Present on many types of hematopoietic cells (B cells, T cells, monocytes, macrophages, eosinophils). Primary function appears to be regulation of IgE synthesis by B-cells, with a stimulatory role at low concentrations of IgE and an inhibitory role at high concentrations. Can facilitate phagocytosis of IgE-opsonized antigens.

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FcARI

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CD89. Present on monocytes, macrophages, neutrophils, eosinophils, and Kupffer cells. Cross-linking of the receptor by antigen can activate endocytosis, phagocytosis, inflammatory mediator release, and ADCC. Expression on monocytes is strongly upregulated by bacterial polysaccharide.

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ICAM-1

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ICAM-1 is expressed on epithelial cell surfaces and is up-regulated as a consequence of direct bacterial stimulation or after contact with cytokines such as IL-1, TNF, or IFN-y. It is important in neutrophil migration (Agace 1995).

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IL-1R

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IL-1R is the receptor for IL-1 and IL-18.

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MD-2

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Can significantly enhance LPS –mediated TLR4 activation (Beutler 2000).

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MHC

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T-cells recognize processed antigen plus the major histocompatibility complex (MHC) molecules which act as a marker to inform the T-cell that it is in contact with another cell.

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MHC Class I

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I Heavy polypeptide chain of 44kDa noncovalently linked to a smaller 12kDa polypeptide called B2-microglobulin. There are three different a-chain genes (H-2K, H-2D, and H-2L in mice). Carried by all nucleated cells. Presents endogenous antigen. Typically interacts solely with CD8+ T cells.

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MHC Class II

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Transmembrane glycoprotein consisting of a and b polypeptide chains of molecular weight 34 kDa and 29 kDa. There are two pairs in humans (H2-A and H2-E). Present on B cells, dendritic cells, macrophages, and thymic epithelium. After activation by IFNg, capillary endothelia and epithelial cells in tissues other than the thymus express surface class II and increased class I. Present exogenous antigen. Interact almost exclusively with CD4+ T cells.

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MyD88

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An adaptor protein required for the proper function of some TLRs and IL-1R.

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STAT6

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Regulator of transcription for cytokines such as eotaxins-1, -2, and -3, MDC, TARC, and I-309.

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TIR domains
Toll/IL-1 receptor (TIR) domain.

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They can be found in the cytoplasmic portions of all TLRs, the IL-1 receptor family, and a group of adaptor proteins (such as MyD88, TIRAP, TRIF, TRAM) (Fitzgerald and Chen 2006).

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TIRAP

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also called Mal (MyD88-adaptor-like protein). Its sole function is to recruit MyD88 to the plasma membrane (Fitzgerald and Chen 2006).

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TLRs

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Toll-like receptors. They are pattern recognition receptors which play a role in innate immunity by recognizing pathogen associated molecular patterns (PAMPs). Most TLRs recruit MyD88, but only some recruit TIRAP, TRIF, and TRAM, which gives rise to specificity in signaling. For instance, both TIRAP and MyD88 are required for activation of the NFkB pathway in response to signaling through TLR2 and TLR4, whereas only MyD88 is required for other TLRs and the IL1R (Fitzgerald and Chen 2006).

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TLR2

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The TLR activated by CMV, Measles virus, and HSV-1.

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TLR3

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Recruits TRIF directly to engage the IRF3 and NFkB pathways. Signals solely through TRIF and does not use MyD88(Fitzgerald and Chen 2006).

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TLR4

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TLR activated by LPS, RSV, and mouse mammary tumor virus. Activates NFkB signaling via TIRAP and MyD88. Activates a MyD88-independent response, by recruiting TRAM, which recruits and activates TRIF, which engages the downstream kinase TBK1 to activate IRF3 and induce IFN gene transcription (Fitzgerald and Chen 2006).