As the data accumulates, it becomes obvious that the Standard Model of TCR structure-function relationships is in jeopardy. The proposed Tritope model has become more meaningful and, in any case, is richer in prediction and explanation. This is illustrated here by using the signaling interactions of the TCR as examples. An unsuspected signaling pathway for positive selection, and for alloreactivity, is predicted. Further, crucial data needed to elucidate the structural elements that distinguish signaling for restrictive- versus allo-reactivity are identified.
Keywords: Signaling; Structure-function; TCR.