Understanding crypticity is the key to revealing the pathogenesis of autoimmunity.
In this opinion, we propose that the hierarchy of antigenic determinants within self-antigens is the major influence in molding the potentially autoreactive T-cell repertoire. The well processed and presented determinants constitute a 'dominant self', whereas the poorly processed and/or presented determinants will be invisible to T cells and comprise a 'cryptic self', which we consider a fundamental cornerstone of a theory of autoimmunity. It accounts for the large repertoire of self-reactive clones because a similar hierarchy is established in the thymus and controls positive and negative selection. Furthermore, this residual T-cell repertoire, largely directed against cryptic determinants, will contain some T cells with sufficient affinity for MHC and antigen that enables them to respond under inflammatory conditions, thus facilitating presentation of previously cryptic determinants.
Moudgil
Kamal D
KD
University of Maryland School of Medicine, Department of Microbiology and Immunology, BRB 13-019, 655 W. Baltimore St, Baltimore, MD 21201, USA.
Sercarz
Eli E
EE
D000818:Animals; D015551:Autoimmunity; D006801:Humans; D016056:Immunodominant Epitopes; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016056:Immunodominant Epitopes; D010455:Peptides