The Tritope Model for restrictive recognition of antigen by T-cells

Based on the Tritope Model of the TCR [Cohn, M., 2005c. The Tritope Model for restrictive recognition of antigen by T-cells. I. What assumptions about structure are needed to explain function? Mol. Immunol. 42, 1419-1443], a set of functional and evolutionary problems surrounding restrictive recognition of antigen are discussed. These include the origin of allele-specific recognition, the selection pressures for polygeneism and polymorphism, the TCR signaling interactions, the centrality of effector T-helper (eTh)-dependence for activation, the role of haplotype exclusion, “nonclassical” MHC-elements, alloreactivity versus xenoreactivity, etc. Further, a set of observations believed to support the Standard Model are reinterpreted.