Genetic heterogeneity of DR4 in the Old Order Amish and two new HLA-D specificities.

Seven Old Order Amish families were D and DR typed using the Eighth International Workshop HTC and Dr antisera. Four different DR4 haplotypes were identified in five families, two of which were negative for Dw4 as well as all other known HLA-D alleles. These two "new" D/DR types reacted with all 8W antisera submitted as anti-DRf4, but could be distinguished by their differential reactivity with three non-DR4 antisera 8W1207, 572, and 1074. We have designated these new specificities as DR-Am4.1 and 4.2 Sera 8W1207 and 572 were positive with DR-Am4.1 cells, while 8W1074 defined DR-Am4.2. The complete haplotypes of the new HLA-D/DR specificities were Aw32, Cw5, Bw44, D-Am4,1, DR-Am4.1 and A2, Cw4, Bw35, D-Am4.2, Dr-Am4.2. Homozygous cells of these new variants stimulated each other strongly in MLC. D-Am4.1/DR-Am4.1 represents a new D region allele possibly showing linkage disequilibrium with Bw4.2/DR-Am4.2, the second new variants, was not found in a screening of 31 non-Amish unrelated subjects. It, therefore, appears to have a low gene frequency in the population.