Evidence for an Unlinked Gene Which Modifies HL-A Antigen Expression

In a sibship of seven, three of four individuals who inherited the haplotype W29-W10 showed modified expression of W10. Their lymphocytes were non-reactive in the cytotoxic test with three of four W10 antisera, but strongly reactive with the fourth serum. The fourth sib's cells reacted strongly with all four antisera. Absorption of anti-W10 sera by the modified cells removed cytotoxic activity, indicating the presence of W10 antigenic determinants on those cells. Absorption with W10 negative cells did not remove cytotoxicity to W10 cells. This observation of the CYNAP (cytotoxic negative-absorption positive) phenomenon in multiple family members suggests a genetic modifier of HL-A antigenic expression which is unlinked to the HL-A chromosomal complex.