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 cross-reactivity of PB1 peptide with antigens. PB1 had no effect on T cells specific for I-A(b) and I-E(k), nor did PB1 increase the T cell responses to concanavalin A and staphylococcal enterotoxin B. The strict I-A(d) specificity suggests that PB1 enhances the recognition of antigen-I-A(d) complex by T cell receptor. PB1 bound to I-A(d) weakly. The augmentative effect could be found on other I-A(d)-binding peptides in appropriate conditions; however, PB1 was distinct in its prominently augmentative effect on all the I-A(d)-restricted T cells analyzed. A similar enhancing activity was demonstrated on a synthetic transferrin receptor peptide with minimum affinity for I-A(d). The unusual enhancing 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 PB1 in the immunization mixture also enhanced T cell responses in vivo, suggesting the possibility of using low-affinity peptide to promote specific immunity.