Tapasin augmentation for enhanced immune response

Abstract

Tapasin (Tpn) is a member of the MHC Class I loading complex and functions to bridge the TAP peptide transporter to MHC Class I molecules. Metastatic human carcinomas express low levels of the antigen processing components (APCs) tapasin and TAP, and display few functional surface MHC Class I molecules. As a result, carcinomas are often unrecognizable by effector cytolytic T cells (CTLs). Tpn alone can enhance survival and immunity of mammals against tumors, but additionally, Tpn and TAP can be used together as components of immunotherapeutic vaccine protocols to eradicate tumors.

Description

Background technique [0001] The MHC class I antigen presentation pathway is essential for presentation to CD8 + T cells cross-present tumor antigens to elicit anti-tumor immune responses, and recognize and kill tumor cells through tumor-specific cytotoxic lymphocytes (CTLs) are of great significance. An important component of these two processes is the chaperone protein Tpn (Tpn), a 48 kDa type I membrane glycoprotein that functions to help transport antigenic peptides to class I in the endoplasmic reticulum (ER) molecularly. Mechanisms by which Tpn mediates this function include retention of empty MHC class I molecules in the ER until peptide loading, stabilization of transporters associated with antigen processing proteins (TAPs), bridging of MHC class I antigens to TAPs, and support of affinity peptides Binding to MHC class I antigens. In the presence of Tpn, surface MHC class I molecules are more stable and thus can more efficiently present antigen to CTLs or their prec...

AI Technical Summary

Problems solved by technology

Defective expression of Tpn destabilizes the MHC class I transport complex including TAP1 and TAP2 and reduces the expression of MHC molecules on the cell surface

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