Summary
A subset of antigen contacts contribute disproportionately to affinity(1). This is frequently observed in cases where antibodies against a human antigen lose substantial affinity for orthologs, for example MT-SP1 (200-300x lower binding to mouse(1)) and LAMP-1 (complete abrogation despite one residue difference(2))
See also
1.
Farady CJ, Sellers BD, Jacobson MP, Craik CS. Improving the species cross-reactivity of an antibody using computational design. Bioorganic & Medicinal Chemistry Letters. 2009;19(14):3744–7. Available from: http://dx.doi.org/10.1016/j.bmcl.2009.05.005
2.
Pruvost T, Mathieu M, Dubois S, Maillère B, Vigne E, Nozach H. Deciphering cross-species reactivity of LAMP-1 antibodies using deep mutational epitope mapping and AlphaFold. mAbs. 2023 Feb;15(1). Available from: http://dx.doi.org/10.1080/19420862.2023.2175311