Abstract

Following activation in the periphery, murine CD8+ T cells exhibit a characteristic increased binding of peanut agglutinin (PNA), reflecting an increased expression of hyposialylated O-linked glycans (Galbeta1-3GalNAcalpha-O-Thr/Ser) on the cell surface. In this report, we show that the majority of the PNA receptors expressed on activated CD8+ T cells are carried by CD45. Other glycoproteins (e.g. CD8) and the glycolipid asialo-GM1 also carry PNA receptors, although to a much lesser extent. Analysis of enzymes involved in the sialylation/de-sialylation pathways showed that generation of PNA receptors in activated CD8+ T cells is not due to up-regulation of endogenous sialidases. Instead, our results indicate that the PNA(high) phenotype results from de novo synthesis of CD45 carrying reduced sialylated core 1 O-glycans.

Highlights

  • 30 years ago PNA1 was observed to recognize differentially subpopulations of lymphocytes in the thymus, and it is routinely used as a marker of intrathymic T cell development (Fig. 1) [1,2,3]

  • Increased Expression of peanut agglutinin (PNA)-binding Sites following in Vitro Activation of Peripheral CD8ϩ T Cells—To investigate the molecular nature of PNA receptors and the mechanism of their generation on CD8ϩ T cells, conditions for in vitro activation were established to recapitulate the conversion from the PNAlow to the PNAhigh phenotype observed in vivo [24]

  • In addition to the utility of PNA as a histochemical marker, several reports have provided evidence that the underlying glycosylation changes detected by PNA have functional implications for T cell biology [16, 39], including modulation of the functions of key regulatory molecules such as CD8 (9 –11) and CD45 [14]

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Summary

Introduction

30 years ago PNA1 was observed to recognize differentially subpopulations of lymphocytes in the thymus, and it is routinely used as a marker of intrathymic T cell development (Fig. 1) [1,2,3]. Mature medullar thymocytes express increased levels of a sialyltransferase, ST3Gal I, that sialylates the core 1 O-glycans producing a structure not recognized by PNA, Sia␣2–3Gal␤1–3GalNAc␣Ser/Thr (4 –7). The functional significance of the glycosylation change detected by PNA has been underscored by analysis of ST3Gal I null mice in which T cells are constitutively PNAhigh [7]. These mice exhibit a striking reduction of naive CD8ϩ T cells due to increased apoptosis in the periphery. In principle, the conversion from PNAlow to PNAhigh phenotype following activation of CD8ϩ T cells could be accomplished either by the action of a sialidase or down-regulated expression of a sialyltransferase

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