HLA-B2704, 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 B2705 and B2706

• Published in: Journal of Immunology 2006-11, Vol.177 (10), p.7015-7023
• Main Authors: Montserrat, Veronica, Galocha, Begona, Marcilla, Miguel, Vazquez, Miriam, Lopez de Castro, Jose A
• Format: Article
• Language: English
• Subjects: Alleles; Antigen Presentation - immunology; ATP-Binding Cassette Transporters - physiology; Cell Line; Cell Membrane - immunology; Cell Membrane - metabolism; HLA-B Antigens - biosynthesis; HLA-B Antigens - metabolism; HLA-B Antigens - physiology; HLA-B27 Antigen; Humans; Membrane Transport Proteins - physiology; Proteasome Endopeptidase Complex - physiology; Protein Folding; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.10.7015

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.