• YAKHAK HOEJI
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• v.50 no.4
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• pp.263-267
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• 2006

CD1d is an unique antigen presenting molecule which provides antigenic repertoires to NKT cells. To examine molecules required for CD1d antigen presentation, we determined an interaction between CD1d and several endoplasmic reticulum (ER) resident molecular chaperones by co-immunoprecipitation. Results indicated that calnexin and calreticulin seem to be bound to mouse CD1d, but TAP and tapasin do not bind. Further, we screened an yeat two hybrid system to identify proteins that help mouse CD1d transportation in the cytosol. We found that two proteins, heat shock protein a sub-unit $(Hsp90{\alpha})$ and protein kinase C and casein kinase substrate in neurons 3 (PACSIN-3), interact with CD1d. Future study will be focus on the role of these molecules during the CD1d antigen presentation.

• Korean Journal of Microbiology
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• v.54 no.3
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• pp.222-227
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• 2018

Mycobacterium tuberculosis (MTB)-originated lipid antigen is presented on the antigen-presenting cell surface with CD1b. When monocyte-derived dendritic cells phagocytosed MTB H37Rv (Multiplicity of infection 10, infectivity: 46.89%), the CD1b expression level decreased slowly. Since this was just a live MTB-mediated phenomenon, it was not detected from heat-killed MTB or mycolic acid, which is a unique antigen of MTB. We confirmed that the phosphorylation of CD1b molecules using 2D electrophoresis with staining could phosphorylate and induce the presentation of the lipid antigen using the phagocytosis assay.

• BMB Reports
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• v.47 no.5
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• pp.241-248
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• 2014

CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to ${\alpha}{\beta}$ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of ${\alpha}{\beta}$ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant $V{\alpha}14-J{\alpha}18$ TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire.

• Molecules and Cells
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• v.44 no.5
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• pp.310-317
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• 2021

Cluster of differentiation 1 (CD1) is a family of cell-surface glycoproteins that present lipid antigens to T cells. Humans have five CD1 isoforms. CD1a is distinguished by the small volume of its antigen-binding groove and its stunted A' pocket, its high and exclusive expression on Langerhans cells, and its localization in the early endosomal and recycling intracellular trafficking compartments. Its ligands originate from self or foreign sources. There are three modes by which the T-cell receptors of CD1a-restricted T cells interact with the CD1a:lipid complex: they bind to both the CD1a surface and the antigen or to only CD1a itself, which activates the T cell, or they are unable to bind because of bulky motifs protruding from the antigen-binding groove, which might inhibit autoreactive T-cell activation. Recently, several studies have shown that by producing T_H2 or T_H17 cytokines, CD1a-restricted T cells contribute to inflammatory skin disorders, including atopic dermatitis, psoriasis, allergic contact dermatitis, and wasp/bee venom allergy. They may also participate in other diseases, including pulmonary disorders and cancer, because CD1a-expressing dendritic cells are also located in non-skin tissues. In this mini-review, we discuss the current knowledge regarding the biology of CD1a-reactive T cells and their potential roles in disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.221-227
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• 2014

Background: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. Aims: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. Materials and Methods: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Results: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ${\geq}2$ Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Conclusions: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ${\geq}2$ Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.78-79
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• 2003

T cell activation is initited by the interaction of T cells with antigen-presenting cells (APCs) in the context of peptide antigen. Initial conjugates are formed by binding between lymphocyte-associated antigen-l (LFA-l, also known as CD11a-CD18) and intercellular adhesion molecule-l (ICAM-1), or CD2 and LFA-3, or other pairs of interactive proteins. (omitted)

• YAKHAK HOEJI
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• v.51 no.6
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• pp.482-489
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• 2007

Kaempferitrin, isolated from Kenaf (Hibiscus cannabinus), was examined to evaluate its modulatory effects on antigen-presenting cell functions of macrophages/monocytes such as phagocytosis of foreign materials, up-regulation of costimulatory molecules (CD40, CD80 and CD86), adhesion molecule activation, and antigen processing and presentation. Kaempferitrin strongly blocked up-regulation of CD40, CD80 and CD86, but not pattern recognition receptor (PRR) (e.g., TLR2). It also suppressed functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay, required for T cell-antigen-presenting cell (APC) interaction. Furthermore, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. However, the compound did not diminish phagocytic uptake, an initial step for antigen processing, and ROS generation in RAW264.7 cells. In particular, to understand molecular mechanism of kaempferitrin-mediated inhibition, the regulatory role of LPS-induced signaling events was examined using immunoblotting analysis. Interestingly, this compound dose dependently suppressed the phosphorylation of $I{\kappa}B{\alpha}$, Src, Akt and Syk, demonstrating that it can negatively modulate the activation of these signaling enzymes. Therefore, our data suggested that kaempferitrin may be involved in regulating APC function-relevant immune responses of macrophages and monocytes by regulating intracellular signaling.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.218-223
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• 2007

T cell proliferation is a pivotal to an effective immune response. Cyclin-dependent kinase (cdk) inhibitor, $p27^{kip1}$ is degraded to initiate T cell expansion. In this study, we show that although the expression of $p27^{kip1}$ protein was down-regulated, that of $p21^{cip1}$, another cdk inhibitor, was up-regulated in $CD8^+$ T cells following in vitro stimulation. Ex vivo gB antigen-stimulation following HSV immunization increased $p21^{cip1}$ positive cells that co-expressed IFN-$\gamma$. Moreover, $p21^{cip1}$ was co-expressed with IFN-${\gamma}$ in E7 antigen-stimulated $CD8^+$ T cells, whereas $p27^{kip1}$ was not. Our findings imply a role of $p21^{cip1}$ proteins in antigen-induced effector $CD8^+$ T cells differentiation in vivo.

• IMMUNE NETWORK
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• v.11 no.2
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• pp.114-122
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• 2011

Background: The leukocyte common antigen (CD45) is a transmembrane-type protein tyrosine phosphatase that has five isoforms. Methods: We generated seven murine mAbs against human CD45 by injecting cells from different origins, such as human thymocytes, PBMCs, and leukemic cell lines. By using various immunological methods including flow cytometry, immunohistochemistry, and immunoprecipitation, we evaluated the reactivity of those mAbs to CD45 of thymus as well as tonsil lysates. Furthermore, we transiently transfected COS-7 cells with each of gene constructs that express five human CD45 isoforms respectively, and examined the specificities of the mAbs against the transfected isoforms. Results: In case of thymocytes, lymphocytes, and monocytes, all the seven mAbs demonstrated positive reactivities whereas none was reactive to erythrocytes and platelets. The majority of immune cells in formalin-fixed paraffin-embedded thymus and tonsil tissues displayed strong membranous immunoreactivity, and the main antigen was detected near 220 kDa in all cases. Among the mAbs, four mAbs (AP4, DN11, SHL-1, and P6) recognized a region commonly present in all the five isoforms. One mAb, YG27, recognized four isoforms (ABC, AB, BC, and O). Two mAbs, P1 and P14, recognized the isoforms that contain exon A encoded regions (ABC and AB). Conclusion: In this study, we confirmed that AP4, DN11, SHL-1, YG27 and P6, are mAbs reactive with the CD45 antigen whereas P1 and P14 are reactive with the CD45RA antigen.

• Molecules and Cells
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• v.42 no.3
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• pp.228-236
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• 2019

CD4 T cells differentiate into $ROR{\gamma}t/IL$-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.