Peptide specificity of the Amerindian B*3905 allotype: molecular insight into selection mechanisms driving HLA class I evolution in indigenous populations of the Americas.
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.
Yagüe
J
J
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, Spain.
Ramos
M
M
Ogueta
S
S
Vázquez
J
J
López de Castro
J A
JA
D020816:Amino Acid Motifs; D005006:Ethnicity; D019143:Evolution, Molecular; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D059946:HLA-B39 Antigen; D006639:Histidine / Q000276:immunology; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D007199:Indians, South American / Q000235:genetics*; D008024:Ligands; D010455:Peptides / Q000276:immunology*; D012641:Selection, Genetic; D017421:Sequence Analysis
D015235:HLA-B Antigens; D059946:HLA-B39 Antigen; D008024:Ligands; D010455:Peptides; D006639:Histidine