[Subtypes of the HLA-B27 molecule and association with spondylarthropathies].
HLA-B27 subtypes differ in their ethnic distribution and in their susceptibility to spondylarthropathies (SA). B*2705 and B*2702 are the most frequent disease-associated subtypes in Caucasians as well as B*2704 and B*2707 in Asia while B*2706 in Asia and B*2709 in Sardinia have been reported not to be associated to SA. Differences in antigenic peptide presentation could underlie such behavior. Several studies suggested that a Tyr C-terminal peptide anchor could be found preferentially in disease-associated subtypes and could be therefore one of the criteria in the search of putative arthritogenic peptide(s). We analyzed by HPLC and Edman sequencing peptides eluted from immunopurified HLA-B27 molecules expressed on B-lymphoblastoid cell lines or C1R transfectans of human origin. We focused our work on B*2707, associated with SA in the same geographical area where B*2706 is not. We found the same preference for Leu at the C-terminus in the peptides bound by both subtypes without any significant signal for Tyr. In the same experimental conditions a Tyr C-terminal anchor was found for B*2705, B*2702, B*2704, B*2703 and also for B*2701 and B*2708, 2 rare subtypes for which binding specificity was previously unknown. Comparison of the F-pocket aminoacid composition in these various subtypes showed a correlation between Asp at position 116 and Tyr at the peptide C-terminus. Asp116 is changed for Tyr in B*2706, B*2707 and His in B*2709, all subtypes allowing a Leu C-terminal anchor. Therefore a Tyr C-terminal anchor correlates with the HLA-B27 F-pocket composition rather than with susceptibility to SA.
Toubert
A
A
Laboratoire d'Immunologie et d'Histocompatibilité, Unité INSERM U. 396, Centre G.-Hayem, Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75475 Paris.
Tieng
V
V
Boisgérault
F
F
Dulphy
N
N
Tamouza
R
R
Charron
D
D
D000483:Alleles; D020816:Amino Acid Motifs / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015796:HLA-B27 Antigen / Q000145:classification / Q000235:genetics*; D006801:Humans; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000235:genetics*
D015796:HLA-B27 Antigen