An observation that illustrates most T cell receptor structure-function relationships.

The Standard model of the T cell receptor (TCR) structure-function relationships is based on an analogy with the B cell receptor. Here a single observation is analyzed to show why this appears to be untenable. The Standard model cannot account for allele-specific recognition of theMHC-encoded presenter of peptide (R) by the TCR nor can it adequately explain alloreactivity. The competing framework is based on the assumptions that (1) single V-domains recognize the alleles of R, (2) restrictive reactivity is peptide specific, whereas alloreactivity is peptide unspecific, and (3) the TCR is born in two conformations, which display reciprocal behaviors (see text). In any case, whatever position one takes regarding these two models, competing conceptualizations are of crucial value in guiding experimentation, not to mention creative thinking.