Specific immune responses restored by alteration in carbohydrate chains of surface molecules on antigen‐presenting cells

Abstract

Two class I major histocompatibility (MHC) mutant mouse strains, H-2bm14 and H-2bm6, differ from the strain of origin C57BL/6 (B6, H-2b) in one and two amino acids of the H-2Db and H-2Kb molecule, respectively. The bm14 Db mutation results in specific failure of female bm14 mice to generate a cytotoxic T lymphocyte (Tc) response to the male-specific antigen H-Y. The allospecific Tc response of CD8+ B6T cells against bm6 Kb mutant spleen cells, in contrast to that against other Kb mutants, is absolutely CD4+ T helper cell dependent. Purified CD8+ T cells completely fail to respond. We now report that the inability to mount these specific immune responses is restored by the use of dendritic cells (DC) as antigen-presenting cells (APC). Comparison of MHC expression on various types of APC by cytofluorimetry and quantitative immunoprecipitation showed very high expression of class I and class II MHC molecules on DC. Strikingly, examination of class I and class II molecules by isoelectric focusing revealed qualitative differences as well. We show that the surface MHC class I molecules of DC are present in greater quantity and carry on average fewer sialic acids than the same molecules isolated from other APC types such as spleen cells, lipopolysaccharide blasts or concanavalin A blasts. That sialic acids on cell surface molecules, including MHC, may play a role in antigen presentation is suggested by our finding that removal of sialic acids, by neuraminidase, can restore specific responses to nonresponder APC as well.

Cellular responses to human chondrocytes: absence of allogeneic responses in the presence of HLA-DR and ICAM-1

“…Our ability to detect cell surface molecules wilh MoAb suggests that it is unlikely that a protective halo was masking antigenic molecules and preventing contact with alloreactive PBMC, Qualitative differences in the MHC class I and II molecules of different cell types also occur. Il has recently been shown that dendritic ceils, which are potent APC, possess fewer sialic acid molecules on ihcir surface and that removal of sialic acids by neuraminidase can restore responses to otherwise non-stimulalory APC [61]. Furihermore, as was shown by others for tibroblasts.…”

Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells

“…Since, on the other hand, DC-derived restriction elements were found to be more efficient in stimulating allogeneicTcells than B cell-derived molecules it was proposed that the charge of the sialic acid residues impairs the interaction between the Tcell antigen receptors and the MHC molecules [37]. Although a comparable degree of sialylation of the polymorphic chains and of the invariant chains y and p40 was detectable (Figs.…”

Dendritic Cells Sensitize TCRs through Self-MHC-Mediated Src Family Kinase Activation

“…As a nonmutually exclusive explanation, structural features of MHC class II may exist that are specific for DCs but are not found on other APCs (43). Such a condition may result in an altered MHC class II affinity for TCRs and for CD4 molecules resulting in improved Lck activation.…”