The diverse αβ T cell receptor (TCR) repertoire exhibits versatility in its ability to generate antigen (Ag) receptors capable of interacting with polymorphic Major Histocompatibility Complex (MHC) molecules and monomorphic MHC-I like molecules, including the CD1 and MR1 families. Collectively, these evolutionarily related Ag-presenting molecules present peptides, lipids and vitamin B metabolites for T cell surveillance. Interestingly, whilst common TCR gene usage can underpin recognition of these distinct classes of Ags, it is unclear whether the 'rules' that govern αβTCR-Ag MHC interactions are shared. We highlight recent observations in the context of TCR biases towards MHC and MHC-I like molecules.
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