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Anti-infectious innate and adaptive immune responses
Published in Gabriel Virella, Medical Immunology, 2019
Carl Atkinson, Gabriel Virella
This T-cell subpopulation is predominantly localized to epithelia and appears to recognize and eliminate infected epithelial cells. In humans, there are two major subsets of γ/δ T cells identified by their γ/δ chain. γ/δ1 T cells are predominant in the thymus and epithelial tissues and recognize various stress-related antigens. γ/δ2 T cells constitute the majority of blood γ/δ T cells. Both subsets share a common Vγ9 chain. Human Vγ9/Vδ2+ T cells can be activated by microbial products (e.g., phosphorylated metabolites) as well as by markers of cellular stress released by infected or transformed cells. The activation of γ/δ T cells can be mediated by their T-cell receptors (TCRs) assisted by costimulatory signals from natural killer (NK)-type receptors but do not involve major histocompatibility complex (MHC)–associated presentation of the activating compounds. The γ/δ TCRs also recognize lipid antigens presented by CD1 molecules, in particular CD1d. Once activated, γ/δ T cells show a great degree of plasticity. They can release proinflammatory cytokines, cause cytolysis of infected or transformed cells by the same mechanisms as classical cytotoxic CD8 T cells, and become professional antigen-presenting cells. Thus, γ/δ T cells appear to be one of the bridges between innate and adaptive immunity.
Inherited Abnormalities in Thyroid Hormone Transport Proteins
Published in Geraldo Medeiros-Neto, John Bruton Stanbury, Inherited Disorders of the Thyroid System, 2019
Geraldo Medeiros-Neto, John Bruton Stanbury
The inheritance mode is X chromosome-linked and it is logical to assume that the complete deficiency of TBG is caused by an abnormality directly affecting the gene. Nevertheless, no deviation from the normal pattern was detected in 26 different bands generated by 18 restriction sites which sampled 2% of the total TBG genome.17 Later, as shown in Table 1, four forms of TBG-CD (CD1, CD5, CD6, and CDJ) have been precisely defined at the molecular level.18,19,19a
Human Blood Dendritic Cells
Published in Brian J. Nickoloff, Dermal Immune System, 2019
Peter S. Freudenthal, Gary S. Wood
Dendritic cells express neither CD2 (the LFA-3 ligand) nor CD 1a nor CD 1b, but trace expression of CD1c has been reported.7 Human epidermal Langerhans cells express CD 1a and CD1c, but these antigens are down-modulated in culture as these cells become more like blood dendritic cells. In terms of NK cell markers, blood dendritic cells do not express either CD56 or CD57, and as described above, CD 16 (Fc-γ-RIII) is also not detected by FACS.7 Surface molecules in the family of the integrins, adhesion molecules involved in many aspects of cell-to-cell adhesions and interactions, are expressed at very high levels on the surface of the blood dendritic cell. These extracellular matrix and cell-adhesion receptors integrate the extracellular environment with the cytoskeleton.28 Three separate subgroups of integrins have been identified within the family, and these are distinguished on the basis of the beta chain of these dimeric molecules. Interestingly, blood dendritic cells express both LFA-1 (CD11a) and its ligand ICAM-1 (CD54) at fairly high levels, and they also express high levels of LFA-3 (CD58) which is the receptor for the CD2 molecule on T cells.7 Additionally, CD 18 (the β-2 integrin), CD29 (the β-1 integrin), and CD11c (p150/90) are expressed at relatively high levels, and there is trace expression of CD11b (the C3bi receptor).7 The high levels of expression of a large number of different integrins/adhesins on the surface of dendritic cells correlates with their formidable ability to bind T cells (see Figure 4).
Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers
Published in Immunological Investigations, 2021
Samaneh Soltani, Mahdi Mahmoudi, Elham Farhadi
In humans, the CD1 family have been classified into two groups. Group 1 consists of CD1a, CD1b, and CD1 c, which are expressed on APCs, are able to present various forms of self and microbial lipid antigens to CD4 and CD8 positive, as well as double-negative T cells. In contrast, group 2 consists only of CD1d isoform, which presents an unusual glycosphingolipid (a-galactosylceramide) to NKT cells (Kaczmarek et al. 2017). CD1a is used as a marker of CD34+ derived DCs but has been identified to be expressed on the surface of the dermal DCs and LCs (Fehres et al. 2015). Although both of LCs and CD1a DC cells express CD1a, the LCs are Langerin+, and the CD1a+ DCs are Langerin- (Cernadas et al. 2009). Both of CD1a high and CD1a low dermal DCs express CD4 and macrophage mannose receptor (MMR), but the latter is DC-SIGN positive. Furthermore, CD1a high and CD1a low dermal DCs are gp120 binding positive and therefore are able to bind HIV (Turville et al. 2002). CD101 is one of the surface markers on this subset that is capable of modulating T-cell responses through IL-10 secretion (Clark et al. 2019).
Evolutionary Underpinnings of Innate-Like T Cell Interactions with Cancer
Published in Immunological Investigations, 2019
Maureen Banach, Jacques Robert
CD1d is the most characterized of CD1 genes. In contrast to classical MHC class Ia and nonclassical class Ib, CD1d presents a wide range of lipids or glycolipids as antigens to NKT cells (Adams and Luoma, 2013). Although microbial components were originally considered to be the major antigenic group, self- or neoplastic-derived antigens can also stimulate NKT cells (Porcelli and Modlin, 1999). Furthermore, self-antigens in the context of CD1d presentation are critical for NKT cell development and function (Godfrey et al., 2010). In combination with the non-polymorphic nature of CD1d, the lipid-derived antigens for NKT cell activation opens new and exciting avenues of research for therapeutic approaches (Godfrey et al., 2018; Moody and Suliman, 2017).
Immunological responses to adjuvant vaccination with combined CD1c+ myeloid and plasmacytoid dendritic cells in stage III melanoma patients
Published in OncoImmunology, 2022
Martine Bloemendal, Kalijn F. Bol, Steve Boudewijns, Mark A.J. Gorris, Johannes H.W. de Wilt, Sandra A.J. Croockewit, Michelle M. van Rossum, Anna L. de Goede, Katja Petry, Rutger H.T. Koornstra, Carl Figdor, Winald R. Gerritsen, Gerty Schreibelt, I. Jolanda M. de Vries
Multiple potential advances in the production of the nDC vaccines are incorporated in our trial. First, the mode of maturation for both DC subsets is optimized. DC maturation is crucial for proper T cell activation.13–15 Especially, exposure of DCs to pathogen-associated molecular patterns, such as Toll-like receptor ligands, yields DCs that induce potent T helper 1 and cytotoxic T cell responses.16–19 Conventional DC2s and pDCs express Toll-like receptors 7 and 8, respectively, which can be triggered by single-stranded RNA (ssRNA). We have shown that complexes of ssRNA stabilized with protamine (pR) can activate both cDC2s and pDCs into functional mature DCs, secreting IL-12 and interferon (IFN)α, respectively.20 Second, we showed that a DC subpopulation expressing both CD1c and the monocytic marker CD14, attenuates the induction of T cell responses.21 Therefore, in our trial, we depleted CD14+ cells prior to the positive selection of cDC2s. Third, we expanded the pool of antigens used to load the DCs. We added the cancer-testis antigens (CTA) MAGE-C2, MAGE-A3 and NY-ESO-1 to the previously used tumor-associated antigens (TAA) gp100 and tyrosinase. Both these CTA and TAA are known to be frequently expressed in melanoma tissue.22,23 Besides, antigens binding HLA types other than HLA-A2.1 were added, to enable induction of immunological responses in HLA-A2.1 negative patients. In addition to a broader panel of HLA-restricted peptides, we added peptide pools with overlapping peptides that cover the complete antigen sequence and bind multiple HLA types, both major histocompatibility complex (MHC) class I and II.