MHC structure and autoimmune T cell repertoire development

Recent work has continued to clarify the relationship between MHC structure and thymic selection that leads to peripheral T cell repertoire developmen t in the pathogenesis of autoimmune diseases. Particular attention has been focused on the nonobese diabetic model of autoimmune diabetes, in which a unique MHC class it molecule (I-A(g7)) plays a central role. In the past ye ar, reports on the biochemistry of I-A(g7) - combined with analysis of the role of I-A(g7) in T cell repertoire selection - supper? a model of defecti ve thymic selection as the basis of the association between particular MHC molecules and autoimmune diseases. Analogous work has been done on the stru cture of the human MHC disease-susceptible and -resistant alleles, DQA1*030 1 DQB1*0302 and DQA1*0102 DQB1*0602, and their effect on autoimmune reperto ire selection. Comparison of these results tin naturally occurring, spontan eous autoimmune human and murine diabetes), with results in a variety of tr ansgenic and knockout models, has produced an integrated view of how avidit y considerations in repertoire selection in the thymus could affect predisp osition towards autoimmunity.