Lecture 7- T cell responses

Lecture 7- T cell responses - DCs migrate to a lymph node...

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Unformatted text preview: DCs migrate to a lymph node from the site of antigen capture to prime T cells Once a DC has migrated to a lymph node, it must interact with a T cell through specific contacts to prime the T cell In this manner, information, in the form of a peptide, can be relayed to the T cell However, before this happens, stable contacts need to be established between cells Multiple molecular contacts mediate DC-T cell interactions Most are redundant, meaning that they mediate T cell interactions with various APCs ICAM-3 binding to DC-SIGN appears specific for DCs only These interactions allow for MHC-TCR recognition to occur Stable binding between DCs and T cells occurs in a concerted fashion First, low affinity interactions lead to MHC-TCR engagement, that signals a conformational change that increases the affinity of binding to form more stable contact (shown here for LFA-1/ICAM-1) which can last several days First proposed by Charlie Janeway, for a productive signal to be sent from an APC by a peptide presented on MHC to the correct T cell, 3 signals are required: named signal 1, 2 and 3 First proposed by Charlie Janeway, for a productive signal to be sent from an APC by a peptide presented on MHC to the correct T cell, 3 signals are required: named signal 1, 2 and 3 Signal 1 is the MHC-TCR interaction, which can activate the T cell specific for the peptide antigen being displayed Signal 2, co-stimulatory signals, are required for survival of the T cell In some cases, co-stimulatory molecules can inhibit T cell activation B7.1/B7.2 (also known as CD80 & CD86) binding to CD28 is the most common co-stimulatory signal. It results in a survival signal and prevents anergy or cell death Main function of co-stimulation is to induce interleukin-2 (IL-2) In the absence of signal 2, T cells enter a state of anergy This is to make sure that there is no self reactivity as signal 2, also known as co-stimulatory signals, result from DC activation (e.g. through TLR activation). Tissue cells do not express high amounts of co-stimualatory molecules Productive co-stimulatory signaling between DC and T cell induces the secretion of interleukin-2 (IL-2) from a T cell that expresses a moderate affinity receptor The a-chain of the IL-2 receptor (CD25) is then up-regulated to increase IL-2 responses, which leads to cell proliferation Co-stimulation through B7-CD28 leads...
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This note was uploaded on 01/03/2012 for the course BI 144 taught by Professor List during the Fall '10 term at Caltech.

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Lecture 7- T cell responses - DCs migrate to a lymph node...

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