Recent data suggest that HLA-B locus alleles can evolve quickly in nat
ive South American populations. To investigate further this phenomenon
of new HLA-B variants among Amerindians, we studied samples from anot
her South American tribe, the Cayapa from Ecuador. We selected individ
uals for HLA-B molecular typing based upon their HLA class II typing r
esults. Three new variants of HLA-B39 and one new Variant of HLA-B15 w
ere found in the Cayapa: HLA-B3905, HLA-B*3906, HLA-B*3907, and HLA-B
1522. A total of thirteen new HLA-B alleles have now been found in th
e four South American tribes studied. Each of these four tribes studie
d, including the Cayapa, had novel alleles that were not found in any
of the other tribes, suggesting that many of these new HLA-B alleles m
ay have evolved since the Paleo-Indians originally populated South Ame
rica. Each of these 13 new alleles contained predicted amino acid repl
acements that were located in the peptide binding site. These amino ac
id replacements may affect the sequence motif of the bound peptides, s
uggesting that these new alleles have been maintained by selection. Ne
w allelic variants have been found for all common HLA-B locus antigeni
c groups present in South American tribes with the exception of B48. I
n spite of its high frequency in South American tribes, no evidence fo
r variants of B48 has been found in all the Amerindians studied, sugge
sting that B48 may have unique characteristics among the B locus allel
es.