Crossreactivity of the T-cell receptor

Abstract

In this issue of Immunology Today, Don Mason argues that T cells should be highly degenerate in order to allow an immune response against any T-cell epitope. Because the number of possible epitopes is indeed much larger than the number of T-cell clonotypes in any immune system, we fully agree that each clonotype should recognize many epitopes. However, if the same degeneracy was expressed in terms of a precursor frequency, i.e. the fraction of clonotypes responding to any particular epitope, the T-cell immune response would seem to be specific. Moreover, a sufficient specificity is required because of self-tolerance. The demands of self-tolerance conflict with those of degeneracy, because crossreactive T cells are likely to become functionally deleted during self-tolerance induction.