Capacity of intact proteins to bind to MHC class II molecules

Here we have demonstrated that denatured, but not native protein antigens can interact with Ia molecules. Thus, the failure of native antigens to be recognized as such by T cells appears to be at least in part due to a deficient antigen/Ia interaction. These results also support previous observations that some T cells can recognize denatured antigens without a further processing requirement. Moreover, a striking correlation was observed between the in vitro binding pattern of denatured proteins and the pattern of restriction of T cell responses elicited by immunization with the native antigen, raising the possibility that an unfolding step may actually occur early during in vivo processing and influence the final outcome of Ia-restricted T cell responses.