ABSTRACT
MHC class I (MHC-I) molecules undergo an intricate folding process in order to pick up antigenic peptide to present to the immune system. In recent years, the discovery of a new peptide editor for MHC-I has added an extra level of complexity in our understanding of how peptide presentation is regulated. On top of this, the incredible diversity in MHC-I molecules leads to significant variation in the interaction between MHC-I and components of the antigen processing and presentation pathway. Here, we review our current understanding regarding how polymorphisms in human leukocyte antigen class I molecules influence their interactions with key components of the antigen processing and presentation pathway. A deeper understanding of this may offer new insights regarding how apparently subtle variation in MHC-I can have a significant impact on susceptibility to disease.
Subject(s)
Antigen Presentation/genetics , Antigens/genetics , Histocompatibility Antigens Class I/genetics , Peptides/genetics , Antigen Presentation/immunology , Antigens/immunology , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Humans , Peptides/immunology , Polymorphism, Genetic/geneticsABSTRACT
The peptide editor TAPBPR is the newest member of the major histocompatibility complex class I (MHC-I) antigen processing and presentation pathway. Since 2013, studies have explored the functions and mechanisms of action of this tapasin homolog. Here, we review the key insights gained from structural studies of the TAPBPR:MHC-I complex and the involvement of the TAPBPR loop in peptide exchange. However, despite recent advances, the question still remains: why do we need TAPBPR? The recent appreciation that different MHC-I allotypes vary in their ability to interact with TAPBPR, together with a role for TAPBPR in alternative presentation pathways highlights that much remains unknown concerning the biological need for TAPBPR.
Subject(s)
Antigen Presentation/immunology , Histocompatibility Antigens Class I/immunology , Immunoglobulins/immunology , Membrane Proteins/immunology , Peptides/immunology , HumansABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
The ability to accurately characterize DNA variant proportions using PCR amplification is key to many genetic studies, including studying tumor heterogeneity, 16S microbiome, viral and immune receptor sequencing. We develop a novel generalizable ultrasensitive amplicon barcoding approach that significantly reduces the inflation/deflation of DNA variant proportions due to PCR amplification biases and sequencing errors. This method was applied to immune receptor sequencing, where it significantly improves the quality and estimation of diversity of the resulting library.
