TY - JOUR
T1 - The love and hate relationship of HLA-DM/DO in the selection of immunodominant epitopes
AU - Welsh, Robin A.
AU - Sadegh-Nasseri, Scheherazade
N1 - Funding Information:
This work was supported by grants from NIAID : R21AI101987 , R01AI120634 , and AAI Careers in Immunology Fellowship Award to SS-N.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/6
Y1 - 2020/6
N2 - Successful activation of CD4 T cells is centered around the ability of antigen presenting cells to successfully process, select Class II immunodominant epitopes from exogenous antigens and to present it to cognate T cells. To achieve this, newly synthesized MHC-II molecules are transferred to a specialized compartment which contain both exogenous antigens and the Class II processing machinery. Here in a process known as ‘editing,’ the Class II accessory molecule DM (HLA-DM human; murine H2-M) facilitates the loading and selection of exogenous peptides to MHC class II molecules thereby assuring proper selection of immunodominant epitopes. A second Class II accessory molecule, DO (HLA-DO human; murine H2-O), mainly present in B cells and thymic epithelium also contributes to the selection of immunodominant epitopes. Yet, despite a wealth of mechanistic insights into how DM functions, understanding the contributions of DO to epitope selection has proven to be highly challenging. In this review, we have attempted to discuss published in vitro and in vivo data during the past three years with insights into the biology of DO.
AB - Successful activation of CD4 T cells is centered around the ability of antigen presenting cells to successfully process, select Class II immunodominant epitopes from exogenous antigens and to present it to cognate T cells. To achieve this, newly synthesized MHC-II molecules are transferred to a specialized compartment which contain both exogenous antigens and the Class II processing machinery. Here in a process known as ‘editing,’ the Class II accessory molecule DM (HLA-DM human; murine H2-M) facilitates the loading and selection of exogenous peptides to MHC class II molecules thereby assuring proper selection of immunodominant epitopes. A second Class II accessory molecule, DO (HLA-DO human; murine H2-O), mainly present in B cells and thymic epithelium also contributes to the selection of immunodominant epitopes. Yet, despite a wealth of mechanistic insights into how DM functions, understanding the contributions of DO to epitope selection has proven to be highly challenging. In this review, we have attempted to discuss published in vitro and in vivo data during the past three years with insights into the biology of DO.
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U2 - 10.1016/j.coi.2020.05.007
DO - 10.1016/j.coi.2020.05.007
M3 - Review article
C2 - 32599219
AN - SCOPUS:85087046071
SN - 0952-7915
VL - 64
SP - 117
EP - 123
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
ER -