dc.contributor.author
Álvaro-Benito, Miguel
dc.contributor.author
Freund, Christian
dc.date.accessioned
2020-09-29T07:59:15Z
dc.date.available
2020-09-29T07:59:15Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/28392
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-28142
dc.description.abstract
The nonclassical major histocompatibility complex of class II molecules (ncMHCII) HLA‐DM (DM) and HLA‐DO (DO) feature essential functions for the selection of the peptides that are displayed by classical MHCII proteins (MHCII) for CD4+ Th cell surveillance. Thus, although the binding groove of classical MHCII dictates the main features of the peptides displayed, ncMHCII function defines the preferential loading of peptides from specific cellular compartments and the extent to which they are presented. DM acts as a chaperone for classical MHCII molecules facilitating peptide exchange and thereby favoring the binding of peptide‐MHCII complexes of high kinetic stability mostly in late endosomal compartments. DO on the other hand binds to DM blocking its peptide‐editing function in B cells and thymic epithelial cells, limiting DM activity in these cellular subsets. DM and DO distinct expression patterns therefore define specific antigen presentation profiles that select unique peptide pools for each set of antigen presenting cell. We have come a long way understanding the mechanistic underpinnings of such distinct editing profiles and start to grasp the implications for ncMHCII biological function. DM acts as filter for the selection of immunodominant, pathogen‐derived epitopes while DO blocks DM activity under certain physiological conditions to promote tolerance to self. Interestingly, recent findings have shown that the unexplored and neglected ncMHCII genetic diversity modulates retroviral infection in mouse, and affects human ncMHCII function. This review aims at highlighting the importance of ncMHCII function for CD4+ Th cell responses while integrating and evaluating what could be the impact of distinct editing profiles because of natural genetic variations.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
CD4 + T cell epitope
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
Revisiting nonclassical HLA II functions in antigen presentation
dc.type
Wissenschaftlicher Artikel
dc.title.subtitle
Peptide editing and its modulation
dcterms.bibliographicCitation.doi
10.1111/tan.14007
dcterms.bibliographicCitation.journaltitle
HLA: Immune Response Genetics
dcterms.bibliographicCitation.number
4
dcterms.bibliographicCitation.pagestart
415
dcterms.bibliographicCitation.pageend
429
dcterms.bibliographicCitation.volume
96
dcterms.bibliographicCitation.url
https://doi.org/10.1111/tan.14007
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2059-2310
dcterms.isPartOf.zdb
2844321-4