Report:

Opening a window on T-cell function

Investigator: Marc Davis

Tuesday Jul 24th, 2001

by John Bonner

Microscopic fluorescent beads are being used to shed light on the processes that make up the human body's "sixth sense," according to a leading US immunologist. Mark Davis, Professor of Microbiology and Immunology at Stanford University School of Medicine, described new techniques for investigating a key stage in T-cell activation that kick-starts the immune response. He has been looking at the events that occur when a T cell forms an immunological synapse - an intimate and long lasting connection with an antigen presenting cell (APC), such as a B-cell or a macrophage. An APC displays peptides on its surface that it has processed from an ingested microbe. It then presents the peptide to T cells, programming them to recognize that antigen in future.

Davis has generated antigen-presenting B cells that present peptide in conjunction with fluorescent plastic beads 20 nanometres in diameter. The interactions between these B cells with T-cells have been filmed with a video microscope during a crucial stage in the formation of the immunological synapse. The T cell binds loosely to the B cell and scans its surface, drawing peptides towards the site where the two cells are in contact using the molecular myosin "motor" of the T-cell cytoskeleton.

If the T cell encounters foreign antigen of sufficient quantity and quality to generate an immune response it starts the process of synapse formation by absorbing calcium ions. If not, the cell detaches and goes looking for another target. Davis' team is hoping to quantify the characteristics of the peptides needed to initiate synapse formation. The numbers of beads grouped around the contact site give an indication of how much antigen is present. Davis admits that the relationship between bead numbers and the peptide is not yet known precisely, but their calculations are becoming finely tuned as the team develops ever-smaller probes.

The particular advantage of using the bead-peptide conjugate is that it shows clearly how the peptide is being processed. "Normally the peptide is invisible and part of the problem has been that we can not see what the T cell is seeing," said Davis.

Davis says the processes that are now being revealed fully justify the analogy with nerve function used when the phrase "immunological synapse" was coined.

"At first, I was opposed to the term but now I am sold on it. You have these T cells looking around for things to do - it's as if they are using a sixth sense," he said.

"It seems to me that what we are seeing is like neurobiology - you present a defined stimulus at a sub-threshold level but still something happens," he concluded. "The response that occurs seems designed to find more of that stimulus. If it does, the T cell will go on to form an immunological synapse, and if doesn't it just goes away. It's really a sensory process."