iNKT-cell responses to glycolipids

Vrajesh V Parekh1, Michael T Wilson, Luc Van Kaer

  • 1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Invariant natural killer T (iNKT) cells are an unusual group of T lymphocytes that recognize glycolipid antigens presented by the major histocompatibility complex class I-related protein CD1d. Because iNKT cells play a regulatory role in the immune system, they are attractive targets for immunotherapy. The marine-sponge-derived glycolipid alpha-galactosylceramide (alpha-GalCer) potently activates iNKT cells. In vivo administration of alpha-GalCer to mice or humans results in rapid and robust cytokine secretion by iNKT cells, followed by the activation of a variety of cell types of the innate and adaptive immune systems. These potent immunomodulatory activities of alpha-GalCer are being exploited for therapeutic purposes. Preclinical studies in mice have demonstrated that alpha-GalCer and related glycolipids can protect mice against a variety of diseases, including cancer, infections, and several autoimmune and inflammatory conditions. Although alpha-GalCer treatment of mice is associated with unwanted side-effects, it has been proven safe in clinical trials with cancer patients. These studies have raised significant enthusiasm for the development of effective and safe iNKT-cell-based immunotherapies for a variety of human diseases.

Related Concept Videos

Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...