TY - JOUR
T1 - Sialylation of N-Linked glycans influences the immunomodulatory effects of IgM on T cells
AU - Colucci, Manuela
AU - Stöckmann, Henning
AU - Butera, Alessia
AU - Masotti, Andrea
AU - Baldassarre, Antonella
AU - Giorda, Ezio
AU - Petrini, Stefania
AU - Rudd, Pauline M.
AU - Sitia, Roberto
AU - Emma, Francesco
AU - Vivarelli, Marina
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Human serum IgM Abs are composed of heavily glycosylated polymers with five glycosylation sites on the m (heavy) chain and one glycosylation site on the J chain. In contrast to IgG glycans, which are vital for a number of biological functions, virtually nothing is known about structure-function relationships of IgM glycans. Natural IgM is the earliest Ig produced and recognizes multiple Ags with low affinity, whereas immune IgM is induced by Ag exposure and is characterized by a higher Ag specificity. Natural anti-lymphocyte IgM is present in the serum of healthy individuals and increases in inflammatory conditions. It is able to inhibit T cell activation, but the underlying molecular mechanism is not understood. In this study, to our knowledge, we show for the first time that sialylated N-linked glycans induce the internalization of IgM by T cells, which in turn causes severe inhibition of T cell responses. The absence of sialic acid residues abolishes these inhibitory activities, showing a key role of sialylated N-glycans in inducing the IgM-mediated immune suppression.
AB - Human serum IgM Abs are composed of heavily glycosylated polymers with five glycosylation sites on the m (heavy) chain and one glycosylation site on the J chain. In contrast to IgG glycans, which are vital for a number of biological functions, virtually nothing is known about structure-function relationships of IgM glycans. Natural IgM is the earliest Ig produced and recognizes multiple Ags with low affinity, whereas immune IgM is induced by Ag exposure and is characterized by a higher Ag specificity. Natural anti-lymphocyte IgM is present in the serum of healthy individuals and increases in inflammatory conditions. It is able to inhibit T cell activation, but the underlying molecular mechanism is not understood. In this study, to our knowledge, we show for the first time that sialylated N-linked glycans induce the internalization of IgM by T cells, which in turn causes severe inhibition of T cell responses. The absence of sialic acid residues abolishes these inhibitory activities, showing a key role of sialylated N-glycans in inducing the IgM-mediated immune suppression.
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U2 - 10.4049/jimmunol.1402025
DO - 10.4049/jimmunol.1402025
M3 - Article
C2 - 25422509
AN - SCOPUS:84919667696
VL - 194
SP - 151
EP - 157
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -