Manipulation of MHC-I/TCR Interaction for Immune Therapy

Abstract

Adoptive immunotherapy involving the transfer of autologous tumor or virus-reactive T lymphocytes has been demonstrated to be effective in the eradication of cancer and virally infected cells. Identification of MHC-restricted antigens and progress in generation of adaptive immune responses have provided new direction for such treatment for severe pathologies such as cancer and autoimmune diseases. Here we review the latest development about the molecular basis of MHC-I/TCR interaction, and its manipulation including enhanced MHC-I expression, modification of peptide and engineered TCR for clinical applications such as vaccine design, tumor therapy and autoimmune diseases.

Glossary

MHC

major histocompatibility complex

MHC-I

MHC class I molecules

MHC-II

MHC class II molecules

CTL

CD8⁺ cytotoxic T cell

APC

antigen-presenting cell

DC

dendritic cell

β₂m

beta-2 microglobulin

IFN-_γ

interferon-gamma

TAP

transporter associated with antigen processing

ER

endoplasmic reticulum

CRT

calreticulin

BiP

immunoglobulin binding protein

TCR

T-cell receptor

pMHC-I

peptide-MHC class I

CDR

complementarity determining region

TIL

tumor-infiltrating lymphocyte

PBMC

peripheral blood mononuclear cell

TAA

tumor associated antigen