Anomalous Mixed Lymphocyte Culture Reactivity between HLA—A, —B, —C, —DR Identical Siblings

Complete HLA typing including HLA--A, --B, --C, --DR (D related B cell typing), --D, mixed lymphocyte culture (MLC), and primed lymphocyte testing (PLT), together with complete red blood cell (RBC), glyoxalase (GLO), GBG (Factor B), and phosphoglucomutase 3 (PGM3) typings were performed on a informative family. The five siblings inherited the four possible combinations of parental HLA haplotypes, and two of the siblings were HLA--A, --B, --C and --DR identical. Repeated MLC testing of the family revealed positive mixed lymphocyte reactivity in all combinations. B cell typing for the DR specificities demonstrated no variation from the expected inheritance pattern and specifically no recombination event. GBG and GLO typings militated against a recombination involving the paternal chromosome. HLA--D testing revealed that only one of the HLA--A, --B, --C, and --DR identical siblings gave typing responses to the HLA--Dw3 specificity present on that maternal haplotype. Utilizing HLA haploidentical combinations, lymphocytes were primed against the four parental haplotypes and the non-Dw3 haplotype of interest (Aw24--B8--DRw3--LDY) in the PLT. The sibling inheriting this haplo-type did not restimulate cells primed against the A2--B40--DRW6--LDY specificity. Furthermore, no discrimination was observed in the restimulation of lymphocytes primed against this haplo-type. Possible interpretations of these family data include: a spontaneous mutation, non-major histocompatibility locus (MHC) stimulation, and HLA--DR/D recombination.