The minimal number of class II MHC-antigen complexes needed for T cell activation

Article Abstract:

In order for foreign proteins (antigens) to be combatted by T cells (a type of cell in the immune system), they must first be ''recognized'' chemically, which only occurs after they have formed a complex with molecules of the major histocompatibility complex (MHC, a region on chromosome 6). MHC molecules are present on virtually all cells in the body, but the cells responsible for presentation of the antigen-MHC complex are white blood cells called antigen-presenting cells (APCs). To better understand how the immune system functions, it is necessary to know how many antigen-MHC complexes are needed before they can be recognized and destroyed by T cells. This was studied in a series of experiments that used a peptide (a short sequence of amino acids) called hen egg lysosome (HEL), known to form complexes with an MHC class II region (the I-Ed determinant) on the APC. T cells were exposed to APCs that had been incubated with various concentrations of HEL, and their production of lymphokine (one measure of T cell activation) measured. In addition, the I-Ed region was purified and allowed to react with different HEL concentrations, and the resulting complexes inserted into cell membranes to stimulate T cell hybridomas (hybrid T cells). Related experiments to test the extent to which the results can be generalized to other APC types were performed. Results showed that only 0.03 percent of purified I- Ed needed to be activated by antigen to induce T-cell activation. Although some APCs were more efficient than others, all cells tested required approximately the same degree of occupancy for stimulation to occur. Macrophages, a white blood cell that scavenges foreign particles, were relatively inefficient. It is likely that the affinity of the T cell receptor (the molecule on the T cell that joins with the antigen-APC complex) is another important determinant of the number of complexes needed for activation. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Presentation of exogenous antigen with class I major histocompatibility complex molecules

Article Abstract:

One type of white blood cell that fights invasion of the body by infectious organisms is the T cell. T cells are programmed to recognize a foreign protein (antigen) when it has formed a chemical complex with molecules on the surface of certain other cells called antigen-presenting cells (APCs). The APC is then said to 'display' the antigen. Antigens, in this context, can be considered to be of two types: those that are present in the fluid surrounding cells (extracellular, or exogenous, antigens), and those that are present or synthesized in the cells themselves (endogenous antigens). The two types are displayed in association with different molecular groups; exogenous antigens are displayed with molecules of the MHC (major histocompatibility complex) class II group, while endogenous antigens are displayed with MHC class I molecules. Class I molecules present antigen to one class of T cell, the cytotoxic (cell-killing) cell, while class II molecules present to helper T cells. However, collaboration between cytotoxic and helper T cells is known to occur. The mechanisms that might facilitate such collaboration were investigated using a T cell hybridoma (cell created by fusing two cells, one of which replicates at a rapid rate) that only recognizes class I MHC molecules. Different APCs were evaluated to determine the conditions under which they could present an exogenous protein antigen (in this case, ovalbumin, OVA) to this hybridoma. Results showed that, under certain conditions, exogenous antigens can be presented by the MHC class I pathway. An APC that can present such antigens in association with class I molecules may thus exist, although it has not been identified. Such a cell could mediate collaboration between helper and cytotoxic T cells. Stimulation of this APC could also be used to increase the cytotoxic T cell response after vaccination. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research

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The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia

Article Abstract:

T cells, one of the white blood cell types active in immunological responding, do not, for the most part, recognize antigen (foreign protein) in isolation. Rather, they recognize antigen as part of a chemical complex with molecules on the surfaces of other cell types that are part of the immune system. Such cells are called antigen-presenting cells (APCs). B cells can function as APCs and can activate T cells of certain types, including those that carry the CD4 molecule on their surfaces (CD4+ T cells). However, much remains to be discovered about the ways B cells present large, complex antigens to stimulate CD4+ and CD8+ (another T cell surface molecule) cytotoxic (cell-killing) T cells. It is possible that B cells play an especially important role in presenting tumor cells to T cells. This was tested in mice infected with FBL tumor cells (containing a viral agent that causes leukemia). FBL cells induce both CD4+ and CD8+ T cell responses, and deplete the B cell population. Results showed a significant reduction in T cell cytotoxic activity in these animals, indicating that B cells play a role in priming T cells. This was noted after the injection of both FBL cells and vaccinia virus (another type of virus). These effects appeared greater for T cells in lymph nodes than T cells in the spleen. Possible mechanisms for the B cell's induction of T cell responses are discussed, as is the role of the B cell as APC. The effects of B cells on T cells may be most important during the induction of the T cells' response, rather than later on, during the expression of its response. One therapeutic implication is that patients with compromised immune systems and reduced T cell function could be helped by treatments that enhance the B cell component. (Consumer Summary produced by Reliance Medical Information, Inc.)

B cells

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