GENETIC AND MOLECULAR DEFINITION OF COMPLEMENTATION GROUP-D IN MHC CLASS-II DEFICIENCY

Four complementation groups, A, B, C and D, have been described among cell lines defective in the coordinate expression of MHC class II gene s. These include cell lines established from patients affected with MH C class II deficiency and experimentally generated mutant cell lines. Group D, in contrast to the other groups, was for a long time represen ted only by the 6.1.6 mutant cell line. The gene responsible for the d efect in this group, RFXAP recently was cloned and found to be mutated in the 6.1.6 cell line and in three patients. Here we report fusion e xperiments in several new HLA class II-deficient patients, completing the classification of the majority of known patients into the four com plementation groups. Patients from five unrelated families were classi fied in complementation group D, while nine others fall into complemen tation groups A and B. None of the patients defined a new complementat ion group. Full correction of MHC class II expression was obtained in cells from patients belonging to group D by transfection with the RFXA P cDNA. The RFXAP coding region was found to be mutated in all patient s. Mutations were found to be recurrent since only three different mut ations have been found in the eight unrelated families reported to dat e.