T cells are not as degenerate as you think, once you get to know them

Abstract

In this review, we dissect two different antigen systems which represent the apparent extremes of T cell receptor (TCR) recognition. In the hemoglobin (Hb) system, a minor change in a single MHC anchor residue disrupts TCR recognition. In the KRN system, a single TCR shows strong reactivity to two peptides from unrelated proteins, presented by different MHC molecules. Upon closer analysis, both turn out to be specific recognition events, following set rules of engagement. Thus, although a TCR can recognize multiple ligands sharing minimal sequence homology, this recognition is still highly specific and is constrained by the same structural requirements. TCR degeneracy is therefore limited and is unlikely to be a major mechanism for autoimmunity.