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Trends Immunol. 2005 Jul;26(7):355-9.

Understanding crypticity is the key to revealing the pathogenesis of autoimmunity.

Author information

1
University of Maryland School of Medicine, Department of Microbiology and Immunology, BRB 13-019, 655 W. Baltimore St, Baltimore, MD 21201, USA.

Abstract

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.

PMID:
15922666
DOI:
10.1016/j.it.2005.05.007
[Indexed for MEDLINE]

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