Seeking better answers to the question of HLA-disease association, de Almeida and Holoshitz have recently put forward a heterodox, Major histocompatibility complex cusp theory at the focus of this theory is a polymorphic region on HLA molecules whose tri-dimensional cusp like shape appears to have been preserved in the entire major histocompatibilty complex family. The theory proposes that the major histocompatibility complex codes for allele-specific ligands in the cusp region, which interact with non HLA-receptors and activate various pathway. Aberrations in those pathways could cause HLA-associated disease.
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