Gene conversion. A mechanism to explain HLA-D region and disease association.

In speculating about mechanisms that might give rise to T-cell epitopes appearing within different HLA-DR frameworks, we return to the hypothesis expressed above that suggests that gene-conversion-like events might be involved in shuffling the hypervariable segments of HLA-D region exons into alternative HLA-D region frameworks where they will still be recognized by the T cell (but not typed by conventional serology or mixed lymphocyte typing) as the "disease associated" HLA product. This might well explain the lack of stringent association between rheumatoid arthritis and HLA-DR4. It is possible, through the use of such alloreactive T-cell clones, that we might eventually define subgroups based upon presumed genetic susceptibility markers, which might allow therapeutic or prognostic assignment of patients with seropositive rheumatoid arthritis.