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A Lanzavecchia

Publications and source records attributed to A Lanzavecchia.

166 records · Page 10Linked to original sources
PubMedDate not supplied

Antigen-specific interaction between T and B cells.

It is well known that B cells require T-cell help to produce specific antibody. Classic experiments suggested that antigen-specific helper T cells interact with antigen-specific B cells via an antigen 'bridge', the B cells binding to one determinant on an antigen molecule (the 'hapten'), while the T cells at the same time recognize another determinant (the 'carrier'). T-helper cells bind specifically to antigen-presenting cells (APC), which have picked up and processed the appropriate antigen, and this interaction, like the interaction of T-helper cells with specific B cells, is restricted by products encoded by the major histocompatibility complex (MHC). Whereas conventional APC such as macrophages display no binding specificity for antigen, B cells have clonally distributed antigen-specific surface immunoglobulin receptors which would be expected to enhance their capacity to present antigen to T cells. These findings are difficult to reconcile with the simple 'antigen bridge' mechanism of interaction, because it is hard to visualize how the bimolecular complex (processed antigen plus MHC molecule) on the APC surface can resemble the trimolecular complex (antigen bound to surface immunoglobulin plus MHC molecule) on the B-cell surface. To address this problem, we have cloned and immortalized human antigen-specific B cells with Epstein-Barr virus (EBV) and analysed their interaction with T-cell clones specific for the same antigen. We report here that surface immunoglobulin is indeed involved in the uptake and concentration of antigen, allowing specific B cells to present antigen to T cells with very high efficiency. However, the antigen must first be internalized and processed by specific B cells and it is then presented to T cells in an MHC-restricted manner indistinguishable from that characteristic of conventional APC.

Antibodies, Monoclonal↗
PubMedDate not supplied

Is the T-cell receptor involved in T-cell killing?

It is known that when two populations of cytotoxic T lymphocytes (CTL) are mixed in conditions where antigen recognition can occur in only one direction, killing also proceeds only in the same direction. These data suggest that occupancy of the T-cell receptor (TCR) is required for the expression of the lytic function by effector CTL, but do not establish whether the TCR itself has a role in the killing process. In particular, it is not clear whether the TCR is involved in the actual delivery of the lethal hit to the target cell (either being itself part of the lytic machinery or directing it), or whether TCR occupancy only serves the function of triggering a set of lytic reactions which are themselves nonspecific and not directed by the TCR. The use of mitogenic lectins or mitogenic antibodies, which bypass specific recognition and induce nonspecific killing, also does not help to clarify this issue, since a necessary characteristic of these ligands is that they bind to the TCR complex or to other 'triggering' molecules and probably bridge these structures to the target cell. The present study describes an in vitro system using human T-cell clones which allows us to dissociate the triggering of a CTL from the delivery of the lethal hit, using no externally added ligands. We report that, once triggered by recognition of the specific target, a CTL can kill any other cell that binds to it, indicating that TCR occupancy is required for triggering, but not for the delivery of the lethal hit.

Clone Cells↗