Abstract
Bidentate interaction of a T-cell receptor and CD8alphabeta heterodimer with a peptide-MHCI complex is required for the generation of cytotoxic T-lymphocytes. During thymic development, the modification of CD8beta glycans influences major histocompatibility complex class I binding to T-cell precursors called thymocytes. ES mass spectrometry (MS) and tandem MS/MS analysis were used to identify the changes occurring in the CD8beta-glycopeptides during T-cell development. Several threonine residues proximal to the CD8beta Ig headpiece are glycosylated with core-type 1 O-glycans. Non-sialylated glycoforms are present in immature thymocytes but are virtually absent in mature thymocytes. These results suggest how sialylation in a discrete segment of the CD8beta stalk by ST3Gal-1 sialyltransferase creates a molecular developmental switch that affects ligand binding.
Highlights
Bidentate interaction of a T-cell receptor and CD8␣ heterodimer with a peptide-major histocompatibility complex class I (MHCI) complex is required for the generation of cytotoxic T-lymphocytes
The change in Peanut Agglutinin (PNA) reactivity is attributable to the induction of the ST3Gal-1 sialyltransferase within the hematopoietic compartment that catalyzes the addition of sialic acid (Sia) residues in a ␣2–3 linkage to terminal galactose (Sia␣2–3Gal1–3GalNAc␣Ser-Thr), capping the PNA binding site in medullary thymocytes (Fig. 1, b and c) [18]
In CD8 knock-out mice, for example, CD8␣␣ homodimers are expressed on the surface of thymocytes but fail to support significant MHCI binding activity as assessed by pMHCI tetramers using flow cytometry
Summary
Bidentate interaction of a T-cell receptor and CD8␣ heterodimer with a peptide-MHCI complex is required for the generation of cytotoxic T-lymphocytes. Evidence of this is the increased CD8␣-MHCI avidity of mature thymocytes following treatment with neuraminidase, an enzyme that removes sialic acid residues from cell surface molecules. The change in PNA reactivity is attributable to the induction of the ST3Gal-1 sialyltransferase within the hematopoietic compartment that catalyzes the addition of sialic acid (Sia) residues in a ␣2–3 linkage to terminal galactose (Sia␣2–3Gal1–3GalNAc␣Ser-Thr), capping the PNA binding site in medullary thymocytes (Fig. 1, b and c) [18].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
