Understanding the inheritance of rheumatoid arthritis (RA) has been the quest of intense investigation over the last decade. One major focus of these efforts has been the attempt to identify genes within the class I1 region of the major histocompatibility complex (MHC) that confer susceptibility for disease. These studies have been based largely on finding associations between class I1 serologic specificities and disease. The results have not been simple to interpret, and lucid analysis is made more difficult by the highly complicated nomenclature that is used to describe the class I1 HLA system. The advent of recombinant DNA technology, however, has greatly expanded our knowledge of this system over the last few years and has offered alternative interpretations of disease association data. One such interpretation, the shared epitope hypothesis, has been described previously (1) and is the subject of this review.
To understand the shared epitope hypothesis, one must have some knowledge of the genetic organization of the class I1 region and of the biochemical structure of class I1 molecules. Briefly, the human class I1 region (Figure 1) extends to nearly l , OOO, OOO base pairs, and includes at least 14 different genes. With the exception of DOp and DZa, these genes are generally found in 1 of 3 major subregions: DR, DQ, or DP.
Each subregion contains at least 1 functional a
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