Peptide specificity of the Amerindian B3905 allotype: molecular insight into selection mechanisms driving HLA class I evolution in indigenous populations of the Americas

• Published in: Tissue antigens 2000-11, Vol.56 (5), p.385-391
• Main Authors: Yagüe, J., Ramos, M., Ogueta, S., Vázquez, J., López de Castro, J.A.
• Format: Article
• Language: English
• Subjects: Amerindians; Amino Acid Motifs; B3905; Central America; Ethnic Groups; Evolution, Molecular; Histidine - immunology; histocompatibility antigen HLA; HLA polymorphism; HLA-B Antigens - genetics; HLA-B Antigens - immunology; HLA-B39; HLA-B39 Antigen; Humans; Indians, Central American - genetics; Indians, South American - genetics; Ligands; mass spectrometry; Mexico; peptide motifs; peptides; Peptides - immunology; Selection, Genetic; Sequence Analysis; South America
• ISSN: 0001-2815; 1399-0039
• DOI: 10.1034/j.1399-0039.2000.560501.x

HLA‐B*3905 is apparently restricted to Amerindian populations and presents a wide geographical distribution, from Mexico to Argentina. It differs from B*3901, one of the founder HLA class I alleles of Central and South Amerindians, by a single nucleotide substitution leading to an Asp74Tyr change in the gene product. The peptide specificity of the B*3905 protein was characterized by pool sequence analysis of B*3905‐bound peptides and by sequencing of a set of individual ligands, using electrospray ion trap mass spectrometry. The results indicate a double effect of the B*3905 mutation. First, pocket B specificity was shifted towards an increased preference for His at peptide position 2, which is the main anchor for B39‐bound peptides, relative to B*3901. Second, at peptide position 3 acidic residues were favored, and aromatic residues disfavored, relative to B*3901. These features approach the peptide specificity of B*3905 to B*3801 and B*1509, allotypes absent from Central and South Amerindians. Together with B*3909, B*3905 is the second HLA‐B39 subtype whose polymorphism results in a shift of peptide specificity towards that of HLA‐B allotypes absent from these populations. This suggests that HLA‐B39 evolution in Central and South America may be an antigen‐driven adaptive response, leading to generate antigen‐presenting properties absent from the HLA class I repertoire of the ancestral population.