Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex.

Leukocyte immunoglobulin (Ig)-like receptors (LILRs), also known as CD85 and immunoglobulin-like transcripts (ILTs), play pivotal roles in regulating immune responses. These receptors define an immune checkpoint that immune therapy can target. Through cis or trans interactions with human leukocyte antigen (HLA)-G, the two most abundantly expressed inhibitory LILRs, LILRB1, and LILRB2 (LILRB1/2, also known as CD85j/d and ILT2/4), are involved in immunotolerance in pregnancy and transplantation, autoimmune diseases, and immune evasion by tumors. Although the discrete domains of LILRB1/2 are clear, the assembly mode of the four extracellular Ig-like domains (D1, D2, D3, and D4) remains unknown. Previous data indicate that D1D2 is responsible for binding to HLA class I (HLA-I), but the roles of D3D4 are still unclear. Here, we determined the crystal structure of the four Ig-like domain LILRB2 and four-domain LILRB1 in complex with HLA-G1. The angles between adjacent domains and the staggered assembly of the four domains suggest limited flexibility and limited plasticity of the receptors during ligand binding. The complex structure of four-domain LILRB1 and HLA-G1 supports the model that D1D2 is responsible for HLA-I binding, while D3D4 acts as a scaffold. Accordingly, cis and trans binding models for HLA-I binding to LILRB1/2 are proposed. The geometries of LILRB1/2 in complex with dimeric and monomeric HLA-G1 suggest the accessibility of the dimeric receptor, which in turn, transduces more inhibitory signals. The assembly of LILRB1/2 and its binding to HLA-G1 could aid in the design of immune regulators and benefit immune interference.

Crystal structures of the two membrane-proximal Ig-like domains (D3D4) of LILRB1/B2: alternative models for their involvement in peptide-HLA binding.

Leukocyte immunoglobulin-like receptors (LILRs), also called CD85s, ILTs, or LIRs, are important mediators of immune activation and tolerance that contain tandem immunoglobulin (Ig)-like folds. There are 11 (in addition to two pseudogenes) LILRs in total, two with two Ig-like domains (D1D2) and the remaining nine with four Ig-like domains (D1D2D3D4). Thus far, the structural features of the D1D2 domains of LILR proteins are well defined, but no structures for the D3D4 domains have been reported. This is a very important field to be studied as it relates to the unknown functions of the D3D4 domains, as well as their relative orientation to the D1D2 domains on the cell surface. Here, we report the crystal structures of the D3D4 domains of both LILRB1 and LILRB2. The two Ig-like domains of both LILRB1-D3D4 and LILRB2-D3D4 are arranged at an acute angle (∼60°) to form a bent structure, resembling the structures of natural killer inhibitory receptors. Based on these two D3D4 domain structures and previously reported D1D2/HLA I complex structures, two alternative models of full-length (four Ig-like domains) LILR molecules bound to HLA I are proposed.

LILRA3 binds both classical and non-classical HLA class I molecules but with reduced affinities compared to LILRB1/LILRB2: structural evidence.

Structurally, Group 1 LILR (Leukocyte Immunoglobulin (Ig)-Like Receptor, also known as Ig-like transcripts, ILT; Leukocyte Ig-like receptor, LIR; and CD85) members are very similar in terms of the HLAIs (human leukocyte antigen class I molecules) binding region and were hypothesized that they all bind to HLAIs. As one of the Group 1 LILRs, LILRA3 is the only secretory LILR and may greatly control the inhibitory immune response induced by LILRB1, LILRB2, and other HLA-binding LILR molecules like LILRA1. Nevertheless, little was known about the binding of LILRA3 to HLAIs. In this report, we present the crystal structure of the LILRA3 domain 1 (D1) and evaluate the D1 and D1D2 (domain 1 and domain 2) binding to classical and non-classical HLAIs using BIAcore® surface plasmon resonance analysis (SPR). We found that LILRA3 binds both classical HLA-A*0201 and non-classical HLA-G1 but with reduced affinities compared to either LILRB1 or LILRB2. The polymorphic amino acids and the LILRA3 D1 structure support this notion.

Crystal structure of leukocyte Ig-like receptor LILRB4 (ILT3/LIR-5/CD85k): a myeloid inhibitory receptor involved in immune tolerance.

The myeloid inhibitory receptor LILRB4 (also called ILT3, LIR-5, CD85k), a member of the leukocyte immunoglobulin-like receptors (LILRs/LIRs), is an important mediator of immune tolerance. Up-regulated on tolerogenic dendritic cells, it has been shown to modulate immune responses via induction of T cell anergy and differentiation of CD8(+) T suppressor cells and may play a role in establishing immune tolerance in cancer. Consequently, characterizing the molecular mechanisms involved in LILRB4 function and in particular its structure and ligands is a key aim but has remained elusive to date. Here we describe the production, crystallization, and structure of the LILRB4 ectodomain to 1.7 Å using an expression strategy involving engineering of an additional disulfide bond in the D2 domain to enhance protein stability. LILRB4 comprises two immunoglobulin domains similar in structure to other LILRs; however, the D2 domain, which is most closely related to the D4 domains of other family members, contains 3(10) helices not previously observed. At the D1-D2 interface, reduced interdomain contacts resulted in an obtuse interdomain angle of ∼107°. Comparison with MHC class I binding Group 1 LILRs suggests LILRB4 is both conformationally and electrostatically unsuited to MHC ligation, consistent with LILRB4 status as a Group 2 LILR likely to bind novel non-MHC class I ligands. Finally, examination of the LILRB4 surface highlighted distinctive surface patches on the D1 domain and D1D2 hinge region, which may be involved in ligand binding. These findings will facilitate our attempts to precisely define the role of LILRB4 in the regulation of immune tolerance.

A Case of Epidural Abscess in Middle Cranial Fossa Secondary to Acute Sphenoid Sinusitis

Acute or chronic sinusitis is common disease of ENT. Most cases usually respond to appropriate treatment; however, some cases occasionally progress to the development of serious complication and poor prognosis. The orbital complications are most common complication fallowed by intracranial complications. The incidence of sinogenic intracranial complications is about 3.7-11.0% and these complications are progressively decreasing however the complications occur due to incorrect use of antibiotics, antibiotics resistant pathogens, decreasing host immunity, improper diagnosis and delayed surgical treatment. Therefore the case of epidural abscess in anterior portion of middle cranial fossa secondary to acute sphenoid sinusitis, which was treated with transnasal endoscopic sphenoidotomy and intravenous antibiotics, is being reported.

A Case of Cavernous Hemangioma Originated from the Middle Turbinate / 대한이비인후과학회지

Hemangiomas are common benign soft tissue tumors in the head and neck, but they occur infrequently in the sinonasal cavity. Most of nasal hemangiomas arise from the nasal septum or vestibule and are of capillary type. Only a few arise from the lateral wall of the nose, and these usually are cavernous. Chief symptoms are recurrent epistaxis and nasal obstruction; if the tumor becomes large, it may cause adjacent bony erosion. Cavernous hemangioma shows essentially little tendency to regress, and in adults, it is more common than capillary hemangioma. Consequently, the majority of cavernous hemangiomas require surgery in contrast to their capillary counterparts. We report a case of cavernous hemangioma of middle turbinate in an adult female, together with a review of the literature.

A Case of C1 Inhibitor Deficiency Syndrome / 대한이비인후과학회지

C1 inhibitor (C1 INH) deficiency is characterized by recurrent attacks of angioedema. The disorder may be inherited or acquired, with both types presenting a similar phenotypic picture. The angioedema most frequently affects the extremities, gastrointestinal, genital, facial and, airway swelling. The laryngeal angioedema can compromise the integrity of the upper airway, so its early diagonsis is crucial. Acquired angioedema by C1 deficiency is a rare disorder characterized by adult onset and lack of inheritance of the disease. We experienced a case of angioedema in a 37-year old man. He had no family history of angioedema and laboratory data showed depressed C1 inhibitor levels. With a review of literature, authors report a case of acquired angioedema by C1 inhibitor deficiency who had a history of the recurrent swelling of tongue, lip and, oral buccal mucosa.

A Case Report of Correction of Cryptotia / 대한이비인후과학회지

Cryptotia is a congenital auricular anomaly found more commonly in orientals than whites. It is characterizaed by the invagination of the upper part of the auricle under the temporal skin and deformity of the auricular cartilage. Surgeries to correct cryptotia principally involves addition of skin to the deficient retroauricular sulcus and cartilage plasty. We have developed a surgical method using modified retroauricular flap and have obtained good result without complication. We hereby report a surgical case with discussion and review of literatures.

Fine Needle Aspiration Biopsy and Histopathologic Diagnosis in the Head and Neck Mass / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Fine needle aspiration cytology (FNAC) is a safe and economical biospy technique which is widely applicable to palpable masses as a first-line procedure. Successful FNAC, however, demands high specimen quality and experience on the part of both the aspirator and the pathologist. We compared cytological diagnosis with histopathological diagnosis in the head and neck region, in order to increase accuracy and solve any discrepancy in the two types of diagnoses. MATERIALS AND METHODS: From July 1996 through to July 1998, FNAC were carried out in 830 cases in palpable mass of the head and neck region in the Department of Pathology, Chonnam University Hospital. The major target sites were lymph nodes (61.4%), soft tissues (22.2%), and salivary glands (16.4%). Histopathological diagnoses were performed in 267 cases by surgical methods. Cytological reports were classified into the following diagnostic categories: non-tumor, tumor (benign, malignant: primary or metastatic). RESULTS: In a series of 267 cases, there were 70 non-tumor lesions (26.2%), 197 tumor lesions (73.8%), (benign: 77, malignant: 120). Lymph nodes were the most common anatomic sites for FNAC. The overall diagnostic accuracy, sensitivity and specificity of FNAC were 95.5%, 98.8%, and 94.2% allowed an correct diagnosis between FNAC and histopathology. CONCLUSION: FNAC of the head and neck region is a sensitive and specific diagnostic tool, especially when diagnosing metastatic carcinomas. Four major causes of error were identified: material adequacy criteria, sampling technique, cytological interpretation and limitations in the procedure. In particular, attention must be paid to subtle morphological changes when making detailed clinical pathological observations; this may help avoid discrepancies and achieve the right diagnosis.