scholarly journals Lipid antigens in immunity

2014 ◽  
Vol 395 (1) ◽  
pp. 61-81 ◽  
Author(s):  
C. Marie Dowds ◽  
Sabin-Christin Kornell ◽  
Richard S. Blumberg ◽  
Sebastian Zeissig
Keyword(s):  
T Cells ◽  
Immune System ◽  
Antigen Presentation ◽  
Nuclear Receptors ◽  
Human Metabolism ◽  
Bioactive Lipids ◽  
Inflammatory Signaling ◽  
Lipid Antigens ◽  
Lipid Antigen

Abstract Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity.

scholarly journals New ways to turn on NKT cells

2011 ◽  
Vol 208 (6) ◽  
pp. 1121-1125 ◽  
Author(s):  
Dale Ian Godfrey ◽  
Jamie Rossjohn
Keyword(s):  
T Cells ◽  
Immune System ◽  
Nkt Cells ◽  
The Other ◽  
Microbial Lipid ◽  
Nkt Cell ◽  
Turn On ◽  
Lipid Antigen ◽  
Common House ◽  
Dust Extract

Natural killer T (NKT) cells are CD1d-restricted, lipid antigen–reactive T cells with powerful immunoregulatory potential. The prototypic antigen for NKT cells is a marine sponge–derived glycolipid, α-galactosylceramide (α-GalCer), but this is not normally encountered in the mammalian environment. Thus, there is great interest in the identification of more physiological stimuli for NKT cells, and numerous studies have shown that NKT cells are capable of responding to a range of microbial lipid-based antigens. Two new studies expand our understanding of environmental NKT cell stimuli, with one showing that CD1d-restricted NKT cell antigens are present within common house dust extract (HDE), whereas the other shows that NKT cells can respond to innate stimuli irrespective of the presence of foreign microbial antigens. Collectively, these two investigations indicate that NKT cells are far more likely to encounter foreign antigens, or innate activating signals, than previously recognized, suggesting a more central role for these cells in the immune system.

scholarly journals Molecular basis of mycobacterial lipid antigen presentation by CD1c and its recognition by    T cells

2014 ◽  
Vol 111 (43) ◽  
pp. E4648-E4657 ◽  
Author(s):  
S. Roy ◽  
D. Ly ◽  
N.-S. Li ◽  
J. D. Altman ◽  
J. A. Piccirilli ◽  
...  
Keyword(s):  
T Cells ◽  
Antigen Presentation ◽  
Molecular Basis ◽  
Lipid Antigen

scholarly journals Lipid-Antigen Presentation by CD1d+ B Cells Is Essential for the Maintenance of Invariant Natural Killer T Cells

Immunity ◽  
2012 ◽  
Vol 36 (3) ◽  
pp. 477-490 ◽  
Author(s):  
Anneleen Bosma ◽  
Azza Abdel-Gadir ◽  
David A. Isenberg ◽  
Elizabeth C. Jury ◽  
Claudia Mauri
Keyword(s):  
T Cells ◽  
B Cells ◽  
Antigen Presentation ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Lipid Antigen ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

scholarly journals CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells

2020 ◽  
Author(s):  
Charlotte A. James ◽  
Yuexin Xu ◽  
Melissa S. Aguilar ◽  
Lichen Jing ◽  
Erik D. Layton ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Antigen Recognition ◽  
Receptor Expression ◽  
Jurkat Cells ◽  
Sample Collection ◽  
Lipid Antigens ◽  
Lipid Antigen

ABSTRACTCD4 and CD8 co-receptors define distinct lineages of T cells restricted by major histocompatibility complex (MHC) Class II and I molecules, respectively. Co-receptors interact with the T cell receptor (TCR) at the surface of MHC-restricted T cells to facilitate antigen recognition, thymic selection, and functional differentiation. T cells also recognize lipid antigens presented by CD1 molecules, but the role that CD4 and CD8 play in lipid antigen recognition is unknown. We studied the effect of CD4 and CD8 on the avidity, activation, and function of T cells specific for two CD1b-presented mycobacterial lipid antigens, glucose monomycolate (GMM) and diacylated sulfoglycolipids (SGL). In a human cohort study using SGL-loaded CD1b tetramers, we discovered a hierarchy among SGL-specific T cells in which T cells expressing the CD4 or CD8 co-receptor stain with a higher tetramer mean fluorescence intensity (MFI) than CD4-CD8- T cells. To determine the role of the TCR co-receptor in lipid antigen recognition, we exogenously expressed GMM and SGL-specific TCRs in Jurkat or polyclonal T cells and quantified tetramer staining and activation thresholds. Transduced CD4+ primary T cells bound the lipid-loaded CD1b tetramer with a higher MFI than CD8+ primary T cells, and transduced CD8+ Jurkat cells bound the SGL-CD1b tetramer with higher MFI than CD4-CD8- Jurkat cells. The presence of either co-receptor also decreased the threshold for IFN-γ secretion. Further, co-receptor expression increased surface expression of CD3ε, suggesting a mechanism for increased tetramer binding and activation. Finally, we used single-cell sequencing to define the TCR repertoire and ex vivo functional profiles of SGL-specific T cells from individuals with M.tb disease. We found that CD8+ T cells specific for SGL express canonical markers associated with cytotoxic T lymphocytes, while CD4+ T cells could be classified as T regulatory or T follicular helper cells. Among SGL-specific T cells, only those expressing the CD4 co-receptor also expressed Ki67, suggesting that they were actively proliferating at the time of sample collection. Together, these data reveal that expression of CD4 and CD8 co-receptor modulates TCR avidity for lipid antigen, leading to functional diversity and differences in in vivo proliferation during M.tb disease.

scholarly journals T-Cell Responses to CD1-Presented Lipid Antigens in Humans with Mycobacterium tuberculosis Infection

2003 ◽  
Vol 71 (6) ◽  
pp. 3076-3087 ◽  
Author(s):  
Timo Ulrichs ◽  
D. Branch Moody ◽  
Ethan Grant ◽  
Stefan H. E. Kaufmann ◽  
Steven A. Porcelli
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Peripheral Blood ◽  
T Cell Responses ◽  
Peripheral Blood Lymphocytes ◽  
Blood Samples ◽  
Lipid Antigens ◽  
Cell Responses ◽  
Lipid Antigen

ABSTRACT CD1-restricted presentation of lipid or glycolipid antigens derived from Mycobacterium tuberculosis has been demonstrated by in vitro experiments using cultured T-cell lines. In the present work, the frequency of T-cell responses to natural mycobacterial lipids was analyzed in ex vivo studies of peripheral blood lymphocytes from human patients with pulmonary tuberculosis, from asymptomatic individuals with known contact with M. tuberculosis documented by conversion of their tuberculin skin tests, and from healthy tuberculin skin test-negative individuals or individuals vaccinated with Mycobacterium bovis BCG. Proliferation and gamma interferon enzyme-linked immunospot assays using peripheral blood lymphocytes and autologous CD1+ immature dendritic cells revealed that T cells from asymptomatic M. tuberculosis-infected donors responded with significantly greater magnitude and frequency to mycobacterial lipid antigen preparations than lymphocytes from uninfected healthy donors. By use of these methods, lipid-antigen-specific proliferative responses were minimally detectable or absent in blood samples from patients with active tuberculosis prior to chemotherapy but became detectable in blood samples drawn 2 weeks after the start of treatment. Lipid antigen-reactive T cells were detected predominantly in the CD4-enriched T-cell fractions of circulating lymphocytes, and anti-CD1 antibody blocking experiments confirmed the CD1 restriction of these T-cell responses. Our results provide further support for the hypothesis that lipid antigens serve as targets of the recall response to M. tuberculosis, and they indicate that CD1-restricted T cells responding to these antigens comprise a significant portion of the circulating pool of M. tuberculosis-reactive T cells in healthy individuals with previous exposure to M. tuberculosis.

Lipid antigen presentation in the immune system; lessons learned from CD 1 d knockout mice

1999 ◽  
Vol 169 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Seokmann Hong ◽  
David C. Scherer ◽  
Nagendra Singh ◽  
Sanjeev K. Mendiratta ◽  
Isao Serizawa ◽  
...  
Keyword(s):  
Immune System ◽  
Antigen Presentation ◽  
Knockout Mice ◽  
Lessons Learned ◽  
Lipid Antigen

scholarly journals Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy

2014 ◽  
Vol 2014 ◽  
pp. 1-25 ◽  
Author(s):  
David Escors
Keyword(s):  
T Cells ◽  
Immune System ◽  
Antigen Presentation ◽  
Cancer Immunotherapy ◽  
Clinical Success ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Therapeutic Success ◽  
Specific Effector ◽  
Antigen Presenting

Since the beginning of the 20th century, scientists have tried to stimulate the antitumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical antineoplastic treatments such as surgery, radiotherapy, and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anticancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review, we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy.

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