The cells of a subset of myeloproliferative neoplasms (MPNs), slow-growing blood cancers, have frameshift mutations in their calreticulin (CALR) gene that are associated with the disease. The tail end of this gene’s mutated protein product (CALR^MUT) should be an ideal neoantigen. Yet T cells directed against the CALR^MUT fragment are rarely found in MPN patients. To figure out why, Ludwig MSK’s Taha Merghoub and his colleagues examined the class I MHC genes—which present antigens to T cells—of patients with this kind of MPN.

When T cells see these antigens, they are activated and kill the cells that express them. Merghoub and his colleagues found that these patients tend to lack MHC-I proteins that bind strongly to CALR^MUT neoantigens, which may explain why their mutant cells aren’t eliminated by the immune system before they can cause MPNs. The researchers generated mutant versions of CALR^MUT peptides that bind efficiently to the MHC-I proteins found in these patients but retain the sequences that are recognized by T cell receptors.

Source: Read Full Article