HLA molecules scan the intracellular proteome and present self- or non-self-peptides to immune effector cells. HLA-Ia (HLA-A, HLA-B and HLA-C) are the most polymorphic genes, resulting in various numbers of allelic variants expressed on the surface of almost all nucleated cells. In contrast to HLA-Ia molecules that activate the immune system during pathogenic invasion, the marginal polymorphic HLA-Ib molecules (HLA-E, HLA-F and HLA-G) are upregulated during pathogenic episodes and mediate immune tolerance. A fine tuning between downregulation of HLA-Ia and upregulation of HLA-Ib can be observed through immunological episodes that require to remain unrecognized by immune effector cells. While HLA-Ia molecules collaborate by presenting a wide range of peptides, every HLA-Ib molecule is highly specialized in its protective immune function and seems to be restricted in the presentation of peptides. Additionally, Ia molecules are expressed ubiquitously while the expression of HLA-Ib molecules is strictly restricted to certain tissues and occurs instantly on demand of the cells/tissue that attempt to be hidden from the immune system. The more knowledge becomes available for the function of HLA-Ib molecules; the question emerges if the molecular typing of HLA-Ib molecules would be reasonable to take a decision post treatment for personalized cellular therapies.
Part of the book: Immunogenetics