Cryptic T cell epitopes in polymorphic immunoglobulin regions: evidence for positive repertoire selection during fetal development.

The adult T cell repertoire is the result of positive and negative intrathymic selective processes. Since non-self antigens are not present in the thymus, self peptides are believed to play a role in the thymic T cell selection. T cell lines raised against a peptide from the second complementarity-determining region (CDR2) of the S107 germ-line immunoglobulin (Ig) do not respond to the intact Ig, indicating that in adult animals this CDR2 epitope is cryptic in the context of intact S107 Ig. To show that the response to self Ig peptide is the result of positive selection, the fetal expression of the S107 germ-line Ig was suppressed by maternal anti-idiotype (Id) injection. Id S107-suppressed mice responded poorly to the CDR2 peptide, indicating that S107 Ig selects positively T cells responding to a polymorphic self epitope. Cross-reactivity of cryptic self Ig with non-self epitopes could be a mechanism to increase the T cell repertoire for foreign antigens.