T cells discriminate between Ia antigens expressed on allogeneic accessory cells and B cells: a potential function for carbohydrate side chains on Ia molecules.

Abstract

Previous studies have shown that the peptides obtained from accessory cell and B-cell Ta molecules are identical but that the a chains of B-cell Ia molecules are more extensively sialylated than those of accessory cells. The present studies were designed to determine whether this glycosylation difference can account for the functional difference in the capacity of the two cell types to activate alloreactive T cells. The experimental data show that normal resting B cells lack the capacity to induce DNA synthesis or differentiation in alloreactive T cells. T cells do recognize polymorphisms in B-cell Ia molecules, however, because they can be specifically primed for a subsequent proliferative stimulus of the same haplotype. The mitogenic signal for T cells is delivered by either allogeneic accessory cells or neuraminidase-treated B cells. Therefore, the T-cell receptor(s) may contain a site specific for the nonpolymorphic asialocarbohydrate moiety on the a chains of accessory cell Ia molecules.

Detection of Autoreactive Myelin Proteolipid Protein 139–151-Specific T Cells by Using MHC II (IAs) Tetramers

“…We found NA at 0.7 U/ml as optimum based on cell viability analysis using 7-AAD and tetramer staining (data not shown). NA has been used to enhance B cell function, and it acts by removing the sialic acid from the surface of the cells (22,33). It is suggested that the removal of sialic acid results in a reduction in the net charge of cells in the interacting populations, in our case APC and T cells, which leads to enhanced cell-cell adhesiveness, which is critical for T cell stimulation (22).…”

Carbohydrate Differences in HLA-DR Molecules Synthesized by Alveolar Macrophages and Blood Monocytes1–3

“…Class II molecules can be glycosylated differently in different cell types (12)(13)(14). In the mouse, differential glycosylation has been correlated with differences in antigen-presenting ability (14).…”

“…Splenic adherent cells, which are active antigenpresenting cells, synthesized class II molecules, which were less sialylated than those synthesized by resting B cells (12). The treatment of resting splenic B cells with neuraminidase, to release the extra sialic acid residues, enhanced their ability to stimulate a mixed leukocyte reaction (13). It was concluded that the enhancement seen with neuraminidase resulted from the removal of sialic acid residues from class II molecules on the B cells.…”

Lead influences translational or posttranslational regulation of ia expression and increases invariant chain expression in mouse B cells

“…Evidence has indicated that sialylation of the Ia a-and @chains induces the dissociation of Ii from the Ia complex (29). Furthermore, desialylation of the Ia chains increases their recognition by T cells (37)(38)(39)(40)). Interestingly, low-level Pb exposure impairs normal desialylation of neural cell adhesion molecule (N-CAM) (41), which is developmentally regulated and coincident with postnatal synaptogenesis.…”