Mark Mamula Describes Links Between Modified Proteins and Autoimmunity
Dr. Mark Mamula, Professor of Medicine at Yale University, visited the Barnett Institute on Feb 18 to discuss mechanisms of how protein modifications can induce automimmunity.
Normally the body inhibits immune responses against any "self" antigens -- sequences which are normally present in the proteome. However, if a sequence is modified, for example by an Asp to isoAsp isomerization, the modified sequence can generate an immune response. Further, once immune tolerance has been broken, the immune response will cross-react with the self peptide and mature against self proteins in both modified and unmodified forms. Dr. Mamula showed several cases where they have demonstrated this in Lupus Erythematosis - small nuclear riboproteins and histones - and tabulated several more autoimmune diseases where it is likely to be occurring.
These results refine the question of what events precipitate this autoimmune recognition in vivo, noting that the correlation of autoimmune diseases in identical twins is only 25%, and that Asp to iso-Asp isomerization naturally occurs in most people.
An application of this work is a mechanism of producing anti-cancer vaccines. Results showed an iso-Asp variant of a tolerated antigen from a tumor cell could elicit a strong immune response against the tumor, ameliorating cancer in a mouse model.
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