5knm

Structural highlights

Function

HLAF_HUMAN Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation. Functions in two forms, as a heterotrimeric complex with B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, presents non-canonical self-peptides carrying post-translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory receptor, a major player in maternal-fetal tolerance. Peptide-free OC acts as a ligand for KIR3DS1 and KIR3DL2 receptors (PubMed:28636952). Upon interaction with activating KIR3DS1 receptor on NK cells, triggers NK cell degranulation and anti-viral cytokine production (PubMed:27455421). Through interaction with KIR3DL2 receptor, inhibits NK and T cell effector functions (PubMed:24018270). May interact with other MHC class I OCs to cross-present exogenous viral, tumor or minor histompatibility antigens to cytotoxic CD8+ T cells, triggering effector and memory responses (PubMed:23851683). May play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, may protect motor neurons from astrocyte-induced toxicity (PubMed:26928464).^{[1] [2] [3] [4] [5]}

See Also

• Beta-2 microglobulin 3D structures
• Leukocyte immunoglobulin-like receptor

References

1. ↑ Goodridge JP, Lee N, Burian A, Pyo CW, Tykodi SS, Warren EH, Yee C, Riddell SR, Geraghty DE. HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway. J Immunol. 2013 Aug 15;191(4):1567-77. PMID:23851683 doi:10.4049/jimmunol.1300080
2. ↑ Goodridge JP, Burian A, Lee N, Geraghty DE. HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. J Immunol. 2013 Oct 1;191(7):3553-62. PMID:24018270 doi:10.4049/jimmunol.1300081
3. ↑ Song S, Miranda CJ, Braun L, Meyer K, Frakes AE, Ferraiuolo L, Likhite S, Bevan AK, Foust KD, McConnell MJ, Walker CM, Kaspar BK. Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis. Nat Med. 2016 Apr;22(4):397-403. PMID:26928464 doi:10.1038/nm.4052
4. ↑ Garcia-Beltran WF, Hölzemer A, Martrus G, Chung AW, Pacheco Y, Simoneau CR, Rucevic M, Lamothe-Molina PA, Pertel T, Kim TE, Dugan H, Alter G, Dechanet-Merville J, Jost S, Carrington M, Altfeld M. Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nat Immunol. 2016 Sep;17(9):1067-74. PMID:27455421 doi:10.1038/ni.3513
5. ↑ Dulberger CL, McMurtrey CP, Holzemer A, Neu KE, Liu V, Steinbach AM, Garcia-Beltran WF, Sulak M, Jabri B, Lynch VJ, Altfeld M, Hildebrand WH, Adams EJ. Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors. Immunity. 2017 Jun 20;46(6):1018-1029.e7. doi: 10.1016/j.immuni.2017.06.002. PMID:28636952 doi:http://dx.doi.org/10.1016/j.immuni.2017.06.002
6. ↑ Dulberger CL, McMurtrey CP, Holzemer A, Neu KE, Liu V, Steinbach AM, Garcia-Beltran WF, Sulak M, Jabri B, Lynch VJ, Altfeld M, Hildebrand WH, Adams EJ. Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors. Immunity. 2017 Jun 20;46(6):1018-1029.e7. doi: 10.1016/j.immuni.2017.06.002. PMID:28636952 doi:http://dx.doi.org/10.1016/j.immuni.2017.06.002