A positive mixed lymphocyte culture (MLC) result between siblings typed as HLA-DR4 indicates that there is a reaction occurring due to differences in HLA antigens beyond just the DR4 designation. HLA typing can show that both siblings share the same DR4 allele, but that does not guarantee that they are completely HLA-identical. The concept here involves the intricate nature of HLA polymorphism, where even among individuals who appear to share the same HLA type, there can still be variations in other HLA loci, such as those encoding HLA class I and class II molecules.
This means that even if both siblings express HLA-DR4, they could possess different haplotypes or other non-DR4 alleles that lead to the positive response in the MLC. This proliferative response arises because T cells in one sibling recognize foreign antigens presented by the Sibling 2’s HLA molecules, which differ from their own, igniting an immune response. Thus, the most likely cause of a positive MLC is the fact that the siblings are not HLA-identical despite sharing the same DR4 alleles.
The other options explore mechanisms that do not accurately account for the positive response in