In vivo immunogenetics: from MIC to RAET1 loci

The major histocompatibility complex (MHC) comprises approximately one thousandth of the genome and encompasses its most polymorphic members. This diversity enables the MHC, at the population level, to counteract the extraordinarily diverse microbiological threats. Reviewed here are two separate sets of MHC class I genes: MIC and RAET1. Whilst the former are encoded within the MHC (6p21.3), the latter are located on the opposite arm of the same chromosome (6q24.2-q25.3). Differing from the prototypical class I genes in structure, transcription, diversity and potential function, they both exemplify the versatility of the MHC fold, despite convergence onto a single ligand, the activatory C-type lectin-like receptor, NKG2D. Why the immune system uses two distinct gene families to interact with a unique ligand remains a fascinating question. To answer this question, the reader will be chronologically exposed to the field whilst following a single thread, i.e. genomics and gene diversity.