HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading.
Tapasin is a resident ER protein believed to be critical for antigen presentation by HLA class I molecules. We demonstrate that allelic variation in MHC class I molecules influences their dependence on tapasin for peptide loading and antigen presentation. HLA-B*2705 molecules achieve high levels of surface expression and present specific viral peptides in the absence of tapasin. In contrast, HLA-B*4402 molecules are highly dependent upon human tapasin for these functions, while HLA-B8 molecules are intermediate in this regard. Significantly, HLA-B*2705 like HLA-B*4402, requires tapasin to associate efficiently with TAP (transporters associated with antigen processing). The unusual ability of HLA-B*2705 to form peptide complexes without associating with TAP or tapasin confers flexibility in the repertoire of peptides presented by this molecule. We speculate that these properties might contribute to the role of HLA-B27 in conferring susceptibility to inflammatory spondyloarthropathies.
Peh
C A
CA
Department of Immunology, Allergy and Arthritis, Flinders Medical Centre, Flinders University of South Australia, Bedford Park. ctmi@flinders.edu.au
Burrows
S R
SR
Barnden
M
M
Khanna
R
R
Cresswell
P
P
Moss
D J
DJ
McCluskey
J
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000276:immunology / Q000502:physiology; D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000096:biosynthesis* / Q000235:genetics*; D059948:HLA-B44 Antigen; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D011110:Polymorphism, Genetic; D011485:Protein Binding; D013499:Surface Properties; D014162:Transfection; D001613:beta 2-Microglobulin / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D059948:HLA-B44 Antigen; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; D001613:beta 2-Microglobulin; C107762:tapasin; C071692:TAP2 protein, human