Phosphorylated self-peptides alter human leukocyte antigen class I-restricted antigen presentation and generate tumor-specific epitopes.

Human leukocyte antigen (HLA) class I molecules present a variety of posttranslationally modified epitopes at the cell surface, although the consequences of such presentation remain largely unclear. Phosphorylation plays a critical cellular role, and deregulation in phosphate metabolism is associated with disease, including autoimmunity and tumor immunity. We have solved the high-resolution structures of 3 HLA A2-restricted phosphopeptides associated with tumor immunity and compared them with the structures of their nonphosphorylated counterparts.

Infiltration of a mesothelioma by IFN-gamma-producing cells and tumor rejection after depletion of regulatory T cells.

Depletion of CD4+CD25+Foxp3+ regulatory T cells (CD25+ T(reg)) with an anti-CD25 Ab results in immune-mediated rejection of tolerogenic solid tumors. In this study, we have examined the immune response to a mesothelioma tumor in mice after depletion of CD25+ cells to elucidate the cellular mechanisms of CD25+ T(reg), a subject over which there is currently much conjecture. Tumor rejection was found to be primarily due to the action of CD8+ T cells, although CD4+ cells appeared to play some role.

Control of immune responses by immunoregulatory T cells.

Immunoregulatory T cells play a key role in modifying the immune responses to self antigens, tumor antigens, and pathogenic organisms. This review summarizes recent data on naturally occurring CD4(+) regulatory T cells that constitutively express CD25 (CD25(+)T(reg)). We examine the markers that can be used to differentiate these cells from effector T cells, what is known about their mode of action in controlling the activity of effector T cells, the antigenic specificity of CD25(+)T(reg), and their ability to survive and to be selected in vivo.