HLA-B27 polymorphism at position 116 critically influences the association with TAP/tapasin, intracellular trafficking and conformational homodimers formation.
HLA-B27 confers susceptibility to ankylosing spondylitis but AS disease mechanisms remain unknown. We determined here the effect of polymorphism and tapasin dependence on the expression, intracellular maturation and homodimer formation among HLA-B27 subtypes. We found that B*2709 with a histidine at position 116 was strongly associated with the transporter associated with antigen processing complex, correlated with lower, non-conformational expression on the cell surface, delayed maturation rate and minimal conformational and non-conformational homodimer formation. In contrast, B*2705 showed a low dependence for transporter associated with antigen processing, faster intracellular maturation and increased levels of homodimeric forms. The absence of tapasin significantly influenced the rate of intracellular maturation of B*2709, showing faster transport out of the endoplasmic reticulum, but similar to that of B*2705. All B27 subtypes examined were unable to express conformational homodimeric forms in the absence of tapasin. This study suggests that HLA-B27 polymorphism drives the tapasin dependency, rates of intracellular maturation and expressions of homodimers.
Blanco-Gelaz
M A
MA
Histocompatibility and Transplantation Unit. Hospital Universitario Central de Asturias. 33006 Oviedo, Spain.
Suárez-Alvarez
B
B
Díaz-Peña
R
R
López-Larrea
C
C
D002478:Cells, Cultured; D019281:Dimerization; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D025242:Spondylarthropathies / Q000235:genetics / Q000378:metabolism
D015796:HLA-B27 Antigen; D026901:Membrane Transport Proteins; C107762:tapasin