HLA-A*02 repertoires in three defined population groups from North and Central India: Punjabi Khatries, Kashmiri Brahmins and Sahariya Tribe

The allelic family of HLA-A*02 with a repertoire of approximately 1022 alleles represents the predominant and most heterogeneous group at the HLA-A locus. This remarkable diversity signifies its evolutionary relevance. Its population-specific diversity is attributed to environmental factors and pathogen pressure and can be harnessed in biology and medicine, particularly in disease association and for HLA-based vaccination approaches. We therefore investigated the HLA-A*02 repertoire in two North Indian caste populations, viz Punjabi Khatries (PK, N = 250), Kashmiri Brahmins (KB, N = 160) and a Central Indian tribe Sahariya (ST, N = 100) using Luminex-based high-resolution rSSO method. When required, results were confirmed with high-resolution PCR-SSP and/or next-generation sequencing (NGS). In the three populations evaluated, HLA-A*02 was observed with an overall high phenotypic/allelic frequency, however, A*02 repertoire differed among them. A total of six alleles were observed (A*02: 01,*02: 03,*02: 05,*02: 06,*02: 07 and*02: 11) in the caste groups, compared with four (except*02: 05 and*02: 07) in the tribals. Our striking observation was the high occurrence of A*02: 11 at the repertoire level (80.6% in ST, 39% in PK, 31.8% in KB). Globally, this allele is rare, observed with low frequencies in limited ethnic groups. The primordial A*02: 01 allele, representative A*02 allele in most ethnicities was observed as the second predominant allele (PK = 27.3%, KB = 31.8% and ST = 11.9%). Extremely high occurrence of A*02: 11 in ST may be representation of ancient Austro-Asiatic genetic pool. In caste populations, the observed A*02 repertoire may be a consequence of natural selection and/or admixture from different populations.