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2017 ; 6
(ä): 158
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Recent advances in Major Histocompatibility Complex (MHC) class I antigen
presentation: Plastic MHC molecules and TAPBPR-mediated quality control
#MMPMID28299193
van Hateren A
; Bailey A
; Elliott T
F1000Res
2017[]; 6
(ä): 158
PMID28299193
show ga
We have known since the late 1980s that the function of classical major
histocompatibility complex (MHC) class I molecules is to bind peptides and
display them at the cell surface to cytotoxic T cells. Recognition by these
sentinels of the immune system can lead to the destruction of the presenting
cell, thus protecting the host from pathogens and cancer. Classical MHC class I
molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and
exceptionally polymorphic and have significant sequence diversity. Thus, in most
species, there are many different MHC I allotypes expressed, each with different
peptide-binding specificity, which can have a dramatic effect on disease outcome.
Although MHC allotypes vary in their primary sequence, they share common tertiary
and quaternary structures. Here, we review the evidence that, despite this
commonality, polymorphic amino acid differences between allotypes alter the
ability of MHC I molecules to change shape (that is, their conformational
plasticity). We discuss how the peptide loading co-factor tapasin might modify
this plasticity to augment peptide loading. Lastly, we consider recent findings
concerning the functions of the non-classical MHC I molecule HLA-E as well as the
tapasin-related protein TAPBPR (transporter associated with antigen presentation
binding protein-related), which has been shown to act as a second quality-control
stage in MHC I antigen presentation.