. Author manuscript; available in PMC: 2020 Mar 1.

Published in final edited form as: Immunogenetics. 2019 Jan 26;71(3):189–196. doi: 10.1007/s00251-018-01097-3

Table 1.

A comparison of published evidence for the two hypotheses proposing mechanism of DO function.

DO binds to DM to inhibit its activity	DO works together with DM in fine tuning MHC II repertoire selection
Less CLIP removal and peptide loading with DR by DM/DO complexes than DM alone (Denzin et al. 1997). DO binds to DM at the same interface with which DM contacts DR1 (Guce et al. 2013). Overexpression of DO in dendritic cells protected NOD.DO mice from development of diabetes (Yi et al. 2010) No spontaneous autoimmune phenotypes have been observed in DO- KO mice (Gu et al. 2013).	Enhanced influenza peptide HA(307–319) binding to DR1 or DR4 with DM/DO complexes (Kropshofer et al. 1998). DM/DO complexes co-precipitated with DR (Kropshofer et al. 1998). DM/DO complexes are better at keeping empty DR4 active at low pH (Kropshofer et al. 1998). DO can interact directly with DR molecules in peptide-receptive conformation (Poluektov et al. 2013b). DO-KO mice did not show reduced MHCII-CLIP levels (Brocke et al. 2003; Liljedahl et al. 1998; Perraudeau et al. 2000). Different DOβ variants, despite having different effects on MHCII-CLIP levels, all bind to DM (Denzin et al. 2017). DO has a more dramatic effect on the presentation of epitopes from antigens internalized by the B cell receptor, rather than fluid phase endocytosis (Alfonso et al. 2003) Naïve DO-KO mice spontaneously produce high titers of antinuclear antibodies (Gu et al. 2013).

DO binds to DM to inhibit its activity

DO works together with DM in fine tuning MHC II repertoire selection

Less CLIP removal and peptide loading with DR by DM/DO complexes than DM alone (Denzin et al. 1997).
DO binds to DM at the same interface with which DM contacts DR1 (Guce et al. 2013).
Overexpression of DO in dendritic cells protected NOD.DO mice from development of diabetes (Yi et al. 2010)
No spontaneous autoimmune phenotypes have been observed in DO- KO mice (Gu et al. 2013).

Enhanced influenza peptide HA(307–319) binding to DR1 or DR4 with DM/DO complexes (Kropshofer et al. 1998).
DM/DO complexes co-precipitated with DR (Kropshofer et al. 1998).
DM/DO complexes are better at keeping empty DR4 active at low pH (Kropshofer et al. 1998).
DO can interact directly with DR molecules in peptide-receptive conformation (Poluektov et al. 2013b).
DO-KO mice did not show reduced MHCII-CLIP levels (Brocke et al. 2003; Liljedahl et al. 1998; Perraudeau et al. 2000).
Different DOβ variants, despite having different effects on MHCII-CLIP levels, all bind to DM (Denzin et al. 2017).
DO has a more dramatic effect on the presentation of epitopes from antigens internalized by the B cell receptor, rather than fluid phase endocytosis (Alfonso et al. 2003)
Naïve DO-KO mice spontaneously produce high titers of antinuclear antibodies (Gu et al. 2013).