A PEPTIDE BINDING WEAKLY TO THE MAJOR HISTOCOMPATIBILITY MOLECULE AUGMENTS T-CELL RESPONSES

An I-A(d)-derived peptide PB1 was found to enhance the reactivity of I -A(d)-restricted T cells. The augmentative effect was not due to the c ross-reactivity of PB1 peptide with antigens. PB1 had no effect on T c ells specific for I-A(b) and I-E(k), nor did PB1 increase the T cell r esponses to concanavalin A and staphyloccocal enterotoxin B. The stric t I-A(d) specificity suggests that PB1 enhances the recognition of ant igen-I-A(d) complex by T cell receptor. PB1 bound to I-A(d) weakly. Th e augmentative effect could be found on other I-A(d)-binding peptides in appropriate conditions; however, PB1 was distinct in its prominentl y augmentative effect on all the I-A(d)-restricted T cells analyzed. A similar enhancing activity was demonstrated on a synthetic transferri n receptor peptide with minimum affinity for I-A(d). The unusual enhan cing activity of PB1 may thus be attributed to the low I-A(d) binding affinity. It was postulated that the binding of low-affinity PB1 would not only stabilize I-A(d) structure, but also enhance the binding of other peptides. This was supported by the increased binding of OVA 323 -339 and cI 84-98 to I-A(d) in the presence of PB1. The inclusion of P B1 in the immunization mixture also enhanced T cell responses in vivo, suggesting the possibility of using low-affinity peptide to promote s pecific immunity.