| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, Madrid, Spain
HLA-B*2705 is strongly associated with ankylosing spondylitis (AS) and reactive arthritis. In contrast, B*2709 has been reported to be more weakly or not associated to AS. These two molecules differ by a single amino acid change: aspartic acid in B*2705 or histidine in B*2709 at position 116. In this study, we analyzed the degree of T cell epitope sharing between the two subtypes. Ten allospecific T cell clones raised against B*2705, 10 clones raised against B*2703 but cross-reactive with B*2705, and 10 clones raised against B*2709 were examined for their capacity to lyse B*2705 and B*2709 target cells. The anti-B*2705 and anti-B*2703 CTL were peptide dependent as demonstrated by their failure to lyse TAP-deficient B*2705-T2 transfectant cells. Eight of the anti-B*2705 and five of the anti-B*2703 CTL clones lysed B*2709 targets. The degree of cross-reaction between B*2705 and B*2709 was donor dependent. In addition, the effect of the B*2709 mutation (D116H) on allorecognition was smaller than the effect of the other naturally occurring subtype change at this position, D116Y. These results demonstrate that B*2705 and B*2709 are the antigenically closest HLA-B27 subtypes. Because allospecific T cell recognition is peptide dependent, our results imply that the B*2705- and B*2709-bound peptide repertoires are largely overlapping. Thus, to the extent to which linkage of HLA-B27 with AS is related to the peptide-presenting properties of this molecule, our results would imply that peptides within a relatively small fraction of the HLA-B27-bound peptide repertoire influence susceptibility to this disease.
This article has been cited by other articles:
|
|
 |
|
  P. Kumar, A. Vahedi-Faridi, W. Saenger, E. Merino, J. A. Lopez de Castro, B. Uchanska-Ziegler, and A. Ziegler Structural Basis for T Cell Alloreactivity among Three HLA-B14 and HLA-B27 Antigens J. Biol. Chem., October 23, 2009; 284(43): 29784 - 29797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zernich, A. W. Purcell, W. A. Macdonald, L. Kjer-Nielsen, L. K. Ely, N. Laham, T. Crockford, N. A. Mifsud, M. Bharadwaj, L. Chang, et al. Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion J. Exp. Med., November 8, 2004; (2004) jem.20031680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Webb, N. A. Borg, M. A. Dunstone, L. Kjer-Nielsen, T. Beddoe, J. McCluskey, F. R. Carbone, S. P. Bottomley, M.-I. Aguilar, A. W. Purcell, et al. The Structure of H-2Kb and Kbm8 Complexed to a Herpes Simplex Virus Determinant: Evidence for a Conformational Switch That Governs T Cell Repertoire Selection and Viral Resistance J. Immunol., July 1, 2004; 173(1): 402 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Macdonald, A. W. Purcell, N. A. Mifsud, L. K. Ely, D. S. Williams, L. Chang, J. J. Gorman, C. S. Clements, L. Kjer-Nielsen, D. M. Koelle, et al. A Naturally Selected Dimorphism within the HLA-B44 Supertype Alters Class I Structure, Peptide Repertoire, and T Cell Recognition J. Exp. Med., September 2, 2003; 198(5): 679 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Montserrat, M. Marti, and J. A. L. de Castro Allospecific T Cell Epitope Sharing Reveals Extensive Conservation of the Antigenic Features of Peptide Ligands Among HLA-B27 Subtypes Differentially Associated with Spondyloarthritis J. Immunol., June 1, 2003; 170(11): 5778 - 5785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hulsmeyer, R. C. Hillig, A. Volz, M. Ruhl, W. Schroder, W. Saenger, A. Ziegler, and B. Uchanska-Ziegler HLA-B27 Subtypes Differentially Associated with Disease Exhibit Subtle Structural Alterations J. Biol. Chem., November 27, 2002; 277(49): 47844 - 47853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ramos, A. Paradela, M. Vazquez, A. Marina, J. Vazquez, and J. A. Lopez de Castro Differential Association of HLA-B*2705 and B*2709 to Ankylosing Spondylitis Correlates with Limited Peptide Subsets but Not with Altered Cell Surface Stability J. Biol. Chem., August 2, 2002; 277(32): 28749 - 28756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Purcell, J. J. Gorman, M. Garcia-Peydro, A. Paradela, S. R. Burrows, G. H. Talbo, N. Laham, C. A. Peh, E. C. Reynolds, J. A. Lopez de Castro, et al. Quantitative and Qualitative Influences of Tapasin on the Class I Peptide Repertoire J. Immunol., January 15, 2001; 166(2): 1016 - 1027. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
