T cell Repertoire Profiling and the Mechanism by which HLA-B27 Causes Ankylosing Spondylitis

Purpose of Review Ankylosing spondylitis (AS) is strongly associated with the HLA-B27 gene. The canonical function of HLA-B27 is to present antigenic peptides to CD8 lymphocytes, leading to adaptive immune responses. The 'arthritogenic peptide' theory as to the mechanism by which HLA-B27 induces ankylosing spondylitis proposes that HLA-B27 presents peptides derived from exogenous sources such as bacteria to CD8 lymphocytes, which subsequently cross-react with antigens at the site of inflammation of the disease, causing inflammation. This review describes findings of studies in AS involving profiling of T cell expansions and discusses future research opportunities based on these findings. Recent Findings Consistent with this theory, there is an expanding body of data showing that expansion of a restricted pool of CD8 lymphocytes is found in most AS patients yet only in a small proportion of healthy HLA-B27 carriers. Summary These exciting findings strongly support the theory that AS is driven by presentation of antigenic peptides to the adaptive immune system by HLA-B27. They point to new potential approaches to identify the exogenous and endogenous antigens involved and to potential therapies for the disease.

Automated summary

The expansion of a restricted pool of CD8 lymphocytes is commonly found in AS patients, but only in a small proportion of healthy HLA-B27 carriers. These findings strongly support the theory that AS is driven by the presentation of antigenic peptides to the adaptive immune system by HLA-B27.