Table 1:

Binding mode definitions.

Term	Definition	Examples
Monospecificity	Monospecific binding of AIRs refers to their capacity to bind to a single epitope with a consistent binding interface and binding mode within the apparent affinity ranges for BCRs (KD range ≈ pM-nM) and TCRs (KD range ≈ μM-mM)	Antibodies targeting variable epitopes of SARS-CoV-2 RBD
Broad specificity	Broadly reactive specificities react with epitopes that are generally well conserved but have either minor residue changes or changes to the local structure	Broadly neutralizing antibodies against HIV or influenza viruses; TCRs cross-reactive with nonapeptide and decapeptide of MART-1
Cross-reactive	Recognition of a discrete motif that is shared in antigens that otherwise share little-to-no similarity	BCR and TCR binding to Streptococcal M protein and cardiac myosin; HIV and HCV binding antibodies
Polyreactive (BCR)	Binding to many distinct antigens with diverse motifs using multiple antibody paratopes that interact with diverse epitopes found on different antigen classes (e.g., protein, lipid, glycan)	Antibodies against influenza HA stalk domain; anti-HIV MPER antibodies
Promiscuity (TCR)	Binding to vast numbers of unrelated peptide antigens	TCR 1E6 binding to recognize over 1 million distinct decameric peptides in the context of HLA-A*02:01