Selection of immunodominant epitopes during antigen processing is hierarchical

Molecular Immunology
Scheherazade Sadegh-Nasseri, AeRyon Kim

Abstract

MHC II proteins present processed antigens to CD4 + T cells through a complex set of events and players that include chaperons and accessory molecules. Antigen processing machinery is optimized for the selection of the best fitting peptides, called 'immunodominant epitopes', in the MHC II groove to which, specific CD4 + T cells respond and differentiate into memory T cells. However, due to the complexity of antigen processing, understanding the parameters that lead to immunodominance has proved difficult. Moreover, immunodominance of epitopes vary, depending on multiple factors that include; simultaneous processing of multiple proteins, involvement of multiple alleles of MHC II that can bind to the same antigen, or competition among several suitable epitopes on a single protein antigen. The current dogma assumes that once an antigenic determinant is selected under a specific condition, it would emerge immunodominant wherever it is placed. Here we will discuss some established parameters that contribute to immunodominance as well as some new findings, which demonstrate that slight changes to antigen structure can cause a complete shift in epitope selection during antigen processing and distort the natural immunodominant epitope.

Citations

Nov 28, 2018·Nature Reviews. Immunology·Maria GeorgievaMarc Lipsitch
Sep 9, 2020·Human Vaccines & Immunotherapeutics·Tapasvi ModiAdrian Shepherd
Mar 2, 2021·Frontiers in Microbiology·Judit Giménez-RoigCristina Fillat
May 15, 2021·Frontiers in Immunology·Brendan K Reed, John W Kappler

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