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Download What is the T-cell receptor (TCR)? (abridged
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What is the T-cell receptor (TCR)? (abridged version) Copyright 2017 by the Rector and Visitors of the University of Virginia What is the TCR? (abridged version) Introduction: T-cell with CD3, CD8, CD57 markers and TCR. CD3 CD8 CD57 LGLL is typically diagnosed by the presence of either a T-cell or NK-cell clone in the blood (rarely, both can be present). For T-cell LGLL, the presence of a clone is established by a test called T-cell receptor gene rearrangement test (or TCR test). The TCR is circled in this diagram. If the test cannot confirm that the cells are clones of each other then it may not be LGLL. The TCR is not expressed on an NK-cell, therefore clonality of NK-LGLL is more difficult to establish. However, chromosomal abnormalities or skewed expression of killer-cell immunoglobulin-like receptors (KIRs) may suggest clonality in NK-LGLL. Future content will discuss this topic in more depth. The TCR is a protein that is a receptor. Its job is to recognize a specific antigen. An antigen is a portion of a microbe or an allergen, basically something foreign to the body. Recognition of the antigen will cause an immune response. As an example, LGLL Patient A and Patient B will have the same sequence for the CD3, CD8, or CD57 markers. However, Patient A’s clonally expanded T-cell population will have a unique TCR sequence compared to Patient B. TCR T-cell Copyright 2017 by the Rector and Visitors of the University of Virginia What is the TCR? (abridged version) What does the TCR look like? CD8 CD57 TCR CD3 Outside the cell α β α β T-cell Inside the cell (cytoplasm) After T-cells are produced in the bone marrow, they go to the thymus to mature. This maturation process will include the TCR rearrangement. The TCR is composed of two proteins, which in this case are alpha (α) and beta (β). The α and β proteins are composed of 3 or 4, respectively protein sub units. The unabridged version of this content describes how it is possible to have different combinations of these sub units. This generates a diverse set of T-cells to recognize a variety of foreign things (microbes, allergens, etc). In other words, diversity is the norm. If every T-cell has the same TCR protein subunits, this tells you a T-cell copied itself over and over due to an immune response to a specific antigen (for example, in the case of an infection). In LGLL, this large population of T-cells with the same TCR subunits persist in the bloodstream. Copyright 2017 by the Rector and Visitors of the University of Virginia What is the TCR? (abridged version) The TCR: αβ vs. γδ The αβ version of the TCR was described on the previous page. The αβ type is more common, however another TCR type called γδ can also exist. This type of receptor is made up of gamma (γ) and delta (δ) proteins. These are also composed of subunits, but are different from αβ. The type of TCR that is found in a patient’s diagnostic test is not known to affect prognosis (likely outcome of the disease). It just means some patients create a different TCR type. Below, you can see the TCR now depicted as either an αβ or γδ type. alpha (α) beta (β) Outside the cell Inside the cell (cytoplasm) α β gamma (γ) delta (δ) Outside the cell γ δ Inside the cell (cytoplasm) To visually see how TCR clonality in T-cells differs between LGLL and a healthy individual, you can refer to “What does clonality look like in LGL leukemia?” To get a more in-depth look at the TCR, you can view the unabridged version of this content. Copyright 2017 by the Rector and Visitors of the University of Virginia