HLA-B27 consists of a heavy chain having three adomains,
which noncovalently binds short peptides and
b2-microglobulin (b2m) [1,2]. There are 24 HLA-B27
subtypes currently recognized. The structural patterns
are consistent with B2705 being the ancestral allele and
the other types being generated by small mutations [1].
B2705 is the dominant subtype and is associated with
AS across broad ethnic and geographic boundaries. Of
the subtypes studied to date, it appears that B2706 and
B2709 do not confer susceptibility to AS. Although the
HLA-B27 has remained a center of extensive research,
the mechanism whereby HLA-B27 confers susceptibility
to AS is not well defined. Current hypotheses regarding
the pathogenesis of AS and ReA have sought to incorporate
HLA B27 into mechanistic models.
Several different hypotheses have been proposed. In the
arthritogenic peptide theory, HLA-B27 binds unique peptides
of microbial or self-origin and presents them to
CD8+ Tcells [1]. These peptides usually have an anchor
arginine residue at their second position and the side
chain of arginine is bound in the B pocket of HLA-B27
[2]. It was recently reported that CD4+ T cells may be
involved in class I–restricted immune recognition [3•].
Consequently AS could involve an HLA-B27-restricted
CD8+ T-cell or CD4+ T-cell response to microbial or