Characterisation and functional implications of the two new HLA-G alleles found in Amerindian and Caribbean populations.

Abstract HLA-G polymorphism has been found to be relatively low in all world populations. In the present paper two new HLA-G molecules are described in ancient American natives. A new HLA-G molecule from a Ecuador Amerindian individual (male) showed four codon changes with respect to HLA-G*01:01:01. Silent changes at α1 domain (residue 57, Pro, CCG → CCA) and α2 domain (residue 93, His, CAC → CAT and residue 100, Gly, GGC → GGT) and one productive change in α3 domain (residue 219 changed from Arg to Trp). This α3 change may dramatically alter HLA-G interactions with beta-2 microglobulin, CD8, ILT-2 and ILT-4 ligands present in subsets of T, B, NK, monocytes, macrophages and dentritic cells. Another HLA-G new molecule was found in a woman from Hispaniola Island, Dominican Republic (Sto Domingo): it presented a silent change at α2 domain residue 107, Gly, GGA → GGT and non-silent change at residue 178, Met → Thr (with respect to HLA-G*01:01:01) which is close to class I molecule/clonotypic T cell receptor interaction sites. Functional implications of these findings are discussed.