MyMedR

Displaying all 11 publications

Abstract:

Sort:

Fulltext A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors

Camacho F, Moreno E, Garcia-Alles LF, Chinea Santiago G, Gilleron M, Vasquez A, et al.

Front Immunol, 2020;11:566710.
PMID: 33162982 DOI: 10.3389/fimmu.2020.566710

Lipids, glycolipids and lipopeptides derived from Mycobacterium tuberculosis (Mtb) are presented to T cells by monomorphic molecules known as CD1. This is the case of the Mtb-specific sulfoglycolipid Ac2SGL, which is presented by CD1b molecules and is recognized by T cells found in tuberculosis (TB) patients and in individuals with latent infections. Our group, using filamentous phage display technology, obtained two specific ligands against the CD1b-Ac2SGL complex: (i) a single chain T cell receptor (scTCR) from a human T cell clone recognizing the CD1b-AcSGL complex; and (ii) a light chain domain antibody (dAbκ11). Both ligands showed lower reactivity to a synthetic analog of Ac2SGL (SGL12), having a shorter acyl chain as compared to the natural antigen. Here we put forward the hypothesis that the CD1b endogenous spacer lipid (EnSpacer) plays an important role in the recognition of the CD1b-Ac2SGL complex by specific T cells. To support this hypothesis we combined: (a) molecular binding assays for both the scTCR and the dAbκ11 antibody domain against a small panel of synthetic Ac2SGL analogs having different acyl chains, (b) molecular modeling of the CD1b-Ac2SGL/EnSpacer complex, and (c) modeling of the interactions of this complex with the scTCR. Our results contribute to understand the mechanisms of lipid presentation by CD1b molecules and their interactions with T-cell receptors and other specific ligands, which may help to develop specific tools targeting Mtb infected cells for therapeutic and diagnostic applications.

Matched MeSH terms: Antigens, CD1/genetics; Antigens, CD1/immunology*
Fulltext Selection of phage-displayed human antibody fragments specific for CD1b presenting the Mycobacterium tuberculosis glycolipid Ac2SGL

Camacho F, Sarmiento ME, Reyes F, Kim L, Huggett J, Lepore M, et al.

Int J Mycobacteriol, 2016 06;5(2):120-7.
PMID: 27242221 DOI: 10.1016/j.ijmyco.2015.12.002

OBJECTIVE/BACKGROUND: The development of new tools capable of targeting Mycobacterium tuberculosis (Mtb)-infected cells have potential applications in diagnosis, treatment, and prevention of tuberculosis. In Mtb-infected cells, CD1b molecules present Mtb lipids to the immune system (Mtb lipid-CD1b complexes). Because of the lack of CD1b polymorphism, specific Mtb lipid-CD1b complexes could be considered as universal Mtb infection markers. 2-Stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-α-α'-d-trehalose (Ac2SGL) is specific for Mtb, and is not present in other mycobacterial species. The CD1b-Ac2SGL complexes are expressed on the surface of human cells infected with Mtb. The aim of this study was to generate ligands capable of binding these CD1b-Ac2SGL complexes.
METHODS: A synthetic human scFv phage antibody library was used to select phage-displayed antibody fragments that recognized CD1b-Ac2SGL using CD1b-transfected THP-1 cells loaded with Ac2SGL.
RESULTS: One clone, D11-a single, light-variable domain (kappa) antibody (dAbκ11)-showed high relative binding to the Ac2SGL-CD1b complex.
CONCLUSION: A ligand recognizing the Ac2SGL-CD1b complex was obtained, which is a potential candidate to be further tested for diagnostic and therapeutic applications.

Matched MeSH terms: Antigens, CD1/genetics; Antigens, CD1/immunology*
An immunohistochemical study of CD1a and CD83-positive infiltrating dendritic cell density in cervical neoplasia

Hayati AR, Zulkarnaen M

Int J Gynecol Pathol, 2007 Jan;26(1):83-8.
PMID: 17197902

Cervical carcinoma is the second leading cancer in women in Malaysia, after breast cancer. Human papillomavirus (HPV) has been implicated in the development of dysplasia or cervical intraepithelial neoplasia and progression to squamous cell carcinoma. Because of the confinement of the human papillomavirus infection within the epithelial layer, the presence of dentritic cells or Langerhans cells in epithelial layer of the ectocervix is paramount in producing immune response. The mature dentritic cells express CD83 and high CD40/80/86, whereas the immature cells express CD1a and low CD40/80/86. By identifying CD1a and CD83, theoretically, both immature and mature dentritic cell populations can be studied. In view of the facts, we investigated the infiltrating cell density of mature and immature dentritic cells in cervical neoplasia.

Matched MeSH terms: Antigens, CD1/immunology; Antigens, CD1/metabolism*
Clear cell variant of calcifying epithelial odontogenic tumor without calcification: a rarity

Mutalik VS, Nichat P, Carnelio S, Solomon M, Radhakrishnan R

J Contemp Dent Pract, 2014 Jan 1;15(1):119-21.
PMID: 24939279

Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign, locally aggressive odontogenic epithelial tumor that affects the jaws. Although there are numerous reports on the variants of CEOT, occurrence of clear cells with complete absence of calcification has been a rarity. Histochemical analysis of tumor cells revealed glycogen granules with PAS staining, with absence of CD 1a staining in clear cells, while the amyloid-like deposit associated with clear cells showed green birefringence with Congo red. We report an unusual variant of CEOT occurring in a 27 years old male patient.

Matched MeSH terms: Antigens, CD1/analysis
Fulltext Cutaneous Rosai-Dorfman disease

Khoo JJ, Rahmat BO

Malays J Pathol, 2007 Jun;29(1):49-52.
PMID: 19105329 MyJurnal

Rosai-Dorfman disease (RDD) is a rare benign proliferative disorder of histiocytes in the lymph nodes with or without extranodal involvement. RDD limited to the skin without nodal involvement, known as cutaneous Rosai-Dorfman disease, is very rare. We describe a 34-year-old female with RDD of the skin over the chest. A large nodule with satellite lesions was excised for histopathological examination. Microscopically, there were many large histiocytes (Rosai-Dorfman cells) exhibiting emperipolesis, among many plasma cells, lymphocytes and neutrophils throughout the dermis and the subcutaneous tissue. The histiocytes were immunohistochemically positive for S-100 protein but negative for CD 1a. Physical examination showed no lymphadenopathy or any extra-cutaneous lesions. Serological tests indicated a past infection with Epstein-Barr virus and cytomegalovirus. The diagnosis of cutaneous RDD may be difficult in the absence of associated lymphadenopathy or any specific features of the skin lesion. Hence, not only is histopathological examination required for definitive diagnosis but a high index of suspicion by the clinicians and pathologists is essential to help diagnose this very rare disease.

Matched MeSH terms: Antigens, CD1/biosynthesis
Interactions of domain antibody (dAbκ11) with Mycobacterium tuberculosis Ac2SGL in complex with CD1b

Law CT, Camacho F, Garcia-Alles LF, Gilleron M, Sarmiento ME, Norazmi MN, et al.

Tuberculosis (Edinb), 2019 01;114:9-16.
PMID: 30711162 DOI: 10.1016/j.tube.2018.11.002

Tuberculosis (TB) is the main cause of mortality among all infectious diseases. The presentation of lipids by CD1b molecules and the interactions of the CD1b-lipid complexes with the immune receptors are important for the understanding of the immune response to Mycobacterium tuberculosis (Mtb), and to develop TB control methods. A specific domain antibody (dAbk11) recognizing the complex of CD1b with Mtb sulphoglycolipid (Ac2SGL) had been previously developed. In order to study the interactions of dAbk11 with Ac2SGL:CD1b, the conformation of Ac2SGL within CD1b was first modelled. The orientation of dAbκ11 with Ac2SGL:CD1b was then predicted by a docking experiment and the complex was sampled using molecular dynamics simulation. Data showed that dAbκ11 Tyr32 OH plays a decisive role in interacting with Ac2SGL alkyl tail HO17. The binding free energy calculation showed that Ac2SGL establish strong hydrophobic interactions with dAbκ11. The model also predicted a higher affinity for the natural sulfoglycolipid (Ac2SGL) than the synthetic analogue (SGL12), which was supported by the ELISA data. These results shed light on the likely mechanism of interactions between Ac2SGL:CD1b and dAbκ11, thus making possible to envision the strategies for dAbκ11 optimization for possible future applications.

Matched MeSH terms: Antigens, CD1/immunology*
Fulltext A rare case of solitary unifocal Langerhans cell histiocytosis with orbital extension: Diagnostic dilemma

Addenan M, May CM, Hooi TK, Ismail F, Kamalden TA

Oman J Ophthalmol, 2018 12 7;11(3):284-287.
PMID: 30505126 DOI: 10.4103/ojo.OJO_149_2017

Langerhans cell histiocytosis (LCH) is rarely encountered in ophthalmology practice. It is a spectrum of disorder characterized by accumulation of histiocytes in various tissues. Diagnosis is challenging as it may simulate periorbital hematoma, rhabdomyosarcoma, and neuroblastoma. We report a case of unifocal LCH with orbital extension. Diagnosis was obtained from incisional biopsy, and histopathological examination showed numerous histiocytes with eosinophilic infiltrations. The presence of Langerhans cells was confirmed by the presence of protein S-100, CD1a, and/or Langerin (CD207). Treatment depends on the degree of organ involvement. She responded well to cytotoxic drugs and steroids. This emphasized that prompt tissue diagnosis is crucial for early management.

Matched MeSH terms: Antigens, CD1
Fulltext Importance of clinical and morphological correlations in diagnosing Langerhans cell histiocytosis

Seb, Omayma, Fauzana, K., Aisyah, M.R., Noraidah, M., Noor Hamidah, H.

Medicine & Health, 2018;13(1):220-226.
MyJurnal

Langerhans cell histiocytosis (LCH) is a clonal histiocytic disorder. The variable clinical manifestations from isolated bone lesion to multisystem disease can cause difficulties and delay in diagnosis. We report a 2 years and 8 months-old girl who presented with a 2 weeks history of persistent fever and weight loss associated with progressive abdominal distension. Physical examination revealed pallor, bilateral proptosis, seaborrheic dermatitis over the scalp and hepatosplenomegaly. Skull X-ray demonstrated multiple lytic lesions at the base and the skull vault. Bone marrow morphology showed numerous abnormal Langerhans cells (LCs) and foamy macrophages. The trephine immunohistochemistry (IHC) stains for CD1a, S-100 and CD68 were inconclusive. The diagnosis of multisystem Langerhans cell histiocytosis (MS-LCH) in this patient was based on the clinical presentation, radiological and morphological analysis. She subsequently received chemotherapy and currently she is on maintenance therapy with a good clinical response. LCH is a rare disease and although the IHC was inconclusive, the correlation of clinical, radiological and morphological data are essential for the diagnosis.

Matched MeSH terms: Antigens, CD1
Fulltext Congenital epulis: immunohistochemical findings of 12 cases

Ajura Abdul Jalil, Lukman Md Auzair, Hin, Lau Shin

Archives of Orofacial Sciences, 2015;10(1):34-40.
MyJurnal

Congenital epulis is a fairly rare soft tissue tumour occurring exclusively on the alveolar ridge of newborns. The exact origin of congenital epulis is still debatable. The objective of the study is to determine the clinicopathological features and immunohistochemical findings of congenital epulis. A retrospective study was carried out to determine the clinicopathological features of congenital epulis, diagnosed histologically in the main oral histopathology laboratory in Malaysia from 1967 to 2014. Immunostaining using vimentin, muscle specific actin, smooth muscle antigen, desmin, S100, CD34, CD68 and CD1a was carried out. Twelve cases of congenital epulis were reviewed. All of the patients were females and the presentation age ranged from 2 to 90 days. The patients comprised of 6 Malays, 3 Chinese, 2 Indians and 1 Orang Asli. Most of the cases (n=7) involved the maxillary ridge and presented as pedunculated well-defined lumps (n=8). Excisional biopsy was performed in all cases. Via immunohistochemistry, vimentin expression was observed in all cases; but negative for CD34, muscle specific actin, smooth muscle antigen, and desmin. CD1a and S100 positivity was seen in five cases. The interstitial cells were highlighted by CD68. Although congenital epulis has been first described 130 years ago, the exact nature of its histogenesis remains a mystery.

Matched MeSH terms: Antigens, CD1
Fulltext Dendritic cell distribution in lymphomas

Hussin HN, Zulkifli FN, Phang KS, Cheong SK

Malays J Pathol, 2009 Dec;31(2):105-12.
PMID: 20514853 MyJurnal

Dendritic cells (DC) are specialized antigen presenting cells (APC) that have important roles in host defenses and in generating anti-tumour immune response. Altered frequency and maturation of DC have been reported in malignant tumours. We studied the distribution and maturation status of DC by immunohistochemistry, on the formalin-fixed, paraffin-embedded lymph node tissues of 32 histologically diagnosed lymphomas and 40 inflammatory conditions that were retrieved from the Department of Pathology, UKM Medical Centre, Kuala Lumpur. Our study showed a significant reduction in the total DC counts in the lymphoma tissues compared to the inflammatory conditions. The mature and immature DC counts were both significantly reduced (p = 0.008 and 0.001 respectively), although a greater reduction was observed in mature DC numbers. We also observed compartmentalization of DC where the immature DC were seen within the tumour tissues and the mature DC were more in peri-tumoural areas. Our findings were similar to other reports, suggesting that reduced numbers of DC appears to be a factor contributing to lack of tumour surveillance in these cases.

Matched MeSH terms: Antigens, CD1/metabolism
Cord blood CD34+ cells cultured with FLT3L, stem cell factor, interleukin-6, and IL-3 produce CD11c+CD1a-/c- myeloid dendritic cells

Fadilah SA, Vuckovic S, Khalil D, Hart DN

Stem Cells Dev, 2007 Oct;16(5):849-55.
PMID: 17999605

Methods that allow expansion of myeloid dendritic cells (MDCs) from CD34(+) cells are potentially important for boosting anti-leukemic responses after cord blood (CB) hematopoietic stem cell transplantation (HSCT). We showed that the combination of early-acting cytokines FLT3-ligand (FL), stem cell factor (SCF), interleukin (IL)-3, and IL-6 supported the generation of CD11c(+)CD16() CD1a()/c() MDCs from CB CD34(+) cells or CB myeloid precursors. Early-acting cytokine-derived MDCs were maintained within the myeloid CD33(+)CD14()CD15() precursors with a mean of 4 x 10(6) cells generated from 1-4 x 10(4) CB CD34(+) cells or myeloid precursors after 2 weeks. After 8-12 days of culture the MDCs expressed higher levels of HLA-DR antigen but lower levels of CD40 and CD86 antigen, compared to adult blood MDCs. At this stage of differentiation, the early-acting cytokine-derived MDCs had acquired the ability to induce greater allogeneic T cell proliferation than monocytes or granulocytes derived from same culture. Early-acting cytokine-derived MDCs exposed to the cytokine cocktail (CC) comprising IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and prostaglandin E (PGE)-2, upregulated the surface co-stimulatory molecules CD40 and CD86 and enhanced allogeneic T cell proliferation, as is characteristic of MDCs maturation. The reliable production of MDCs from CB CD34(+) cells provides a novel way to study their lineage commitment pathway(s) and also a potential means of enriching CB with MDCs to improve prospects for DC immunotherapy following CB HSCT.

Matched MeSH terms: Antigens, CD1/metabolism; Antigens, CD11c/metabolism