title: HLA-B*2704, an allotype associated with ankylosing spondylitis, is critically dependent on transporter associated with antigen processing and relatively independent of tapasin and immunoproteasome for maturation, surface expression, and T cell recognition: relationship to B*2705 and B*2706.
abstract: B*2704 is strongly associated to ankylosing spondylitis in Asian populations. It differs from the main HLA-B27 allotype, B*2705, in three amino acid changes. We analyzed the influence of tapasin, TAP, and immunoproteasome induction on maturation, surface expression, and T cell allorecognition of B*2704 and compared some of these features with B*2705 and B*2706, allotypes not associated to disease. In the tapasin-deficient .220 cell line, this chaperone significantly influenced the extent of folding of B*2704 and B*2705, but not their egress from the endoplasmic reticulum. In contrast, B*2706 showed faster folding and no accumulation in the endoplasmic reticulum in the absence of tapasin. Surface expression of B*2704 was more tapasin dependent than B*2705. However, expression of free H chain decreased in the presence of this chaperone for B*2705 but not B*2704, suggesting that more suboptimal ligands were loaded on B*2705 in the absence of tapasin. Despite its influence on surface expression, tapasin had little effect on allorecognition of B*2704. Both surface expression and T cell recognition of B*2704 were critically dependent on TAP, as established with TAP-deficient and TAP-proficient T2 cells. Both immunoproteasome and surface levels of B*2704 were induced by IFN-gamma, but this had little effect on allorecognition. Thus, except for the differential effects of tapasin on surface expression, the tapasin, TAP, and immunoproteasome dependency of B*2704 for maturation, surface expression, and T cell recognition are similar to B*2705, indicating that basic immunological features are shared by the two major HLA-B27 allotypes associated to ankylosing spondylitis in human populations.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Facultad de Ciencias, Universidad Autónoma, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Montserrat
authors.forename: Begoña
authors.initials: B
authors.lastname: Galocha
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcilla
authors.forename: Miriam
authors.initials: M
authors.lastname: Vázquez
authors.forename: José A
authors.initials: JA
authors.lastname: López de Castro
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015796:HLA-B27 Antigen; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D017510:Protein Folding; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D015235:HLA-B Antigens; C510610:HLA-B*27:04 antigen; C464936:HLA-B*27:05 antigen; C510629:HLA-B*27:06 antigen; D015796:HLA-B27 Antigen; D026901:Membrane Transport Proteins; C107762:tapasin; C477327:transporter associated with antigen processing (TAP); D046988:Proteasome Endopeptidase Complex